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1.
World J Gastrointest Oncol ; 16(5): 2159-2167, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38764827

RESUMO

BACKGROUND: The research findings suggest that the prognosis of children with Wilms tumor (WT) is affected by various factors. Some scholars have indicated that loss of heterozygosity (LOH) on chromosome 16q is associated with a poor prognosis in patients with WT. AIM: To further elucidate this relationship, we conducted a meta-analysis. METHODS: This meta-analysis was registered in INPLASY (INPLASY2023100060). We systematically searched databases including Embase, PubMed, Web of Science, Cochrane, and Google Scholar up to May 31, 2020, for randomized trials reporting any intrapartum fetal surveillance approach. The meta-analysis was performed within a frequentist framework, and the quality and network inconsistency of trials were assessed. Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT. RESULTS: Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT (I2 = 25%, P < 0.001). As expected, 16q LOH can serve as an effective predictor of event-free survival in patients with WT (risk ratio = 1.95, 95%CI: 1.52-2.49, P < 0.001). CONCLUSION: In pediatric patients with WT, there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis. Clinical detection of 16q chromosome LOH warrants increased attention to the patient's prognosis.

2.
Eur J Surg Oncol ; 50(7): 108383, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38704898

RESUMO

OBJECTIVE: To evaluate the impact of previous poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor therapy on the effectiveness of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent ovarian cancer (PSROC). METHODS: We identified patients with PSROC who underwent SCS at the Cancer Hospital, Chinese Academy of Medical Science, between January 2010 and December 2022. Postoperative complications within 30 days were categorized using the Accordion Severity Grading System. The Kaplan‒Meier method was used to estimate both overall survival (OS) and progression-free survival (PFS), and multivariate analysis was used to identify independent prognostic factors. RESULTS: Of the 265 patients included, 39 received prior PARP inhibitor therapy (Group A), and 226 did not (Group B). The rates of complete resection after SCS did not significantly differ between the two groups (79.5 % for Group A vs. 81.0 % for Group B; p = 0.766). As of December 2023, Group A exhibited a significantly shorter median PFS (14.2 months) than Group B (22.5 months; p = 0.002). Furthermore, the 3-year OS rate was lower in Group A (72.5 %) than in Group B (82.7 %; p = 0.015). The incidence of severe postoperative complications was comparable between Groups A and B (7.7 % vs. 1.8 %; p = 0.061). Multivariate analysis revealed that prior PARP inhibitor therapy significantly reduced the median PFS (hazard ratio (HR) = 4.434; p = 0.021) and OS (HR = 2.076; p = 0.010). CONCLUSIONS: SCS for PSROC demonstrated reduced efficacy in patients previously treated with PARP inhibitors compared to those without prior PARP inhibitor treatment.

4.
Hortic Res ; 11(5): uhae081, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38766530

RESUMO

BTB and TAZ domain proteins (BTs) function as specialized adaptors facilitating substrate recognition of the CUL3-RING ubiquitin ligase (CRL3) complex that targets proteins for ubiquitination in reaction to diverse pressures. Nonetheless, knowledge of the molecular mechanisms by which the apple scaffold protein MdBT2 responds to external and internal signals is limited. Here we demonstrate that a putative Ca 2+ sensor, calmodulin-like 15 (MdCML15), acts as an upstream regulator of MdBT2 to negatively modulate its functions in plasma membrane H+-ATPase regulation and iron deficiency tolerance. MdCML15 was identified to be substantially linked to MdBT2, and to result in the ubiquitination and degradation of the MdBT2 target protein MdbHLH104. Consequently, MdCML15 repressed the MdbHLH104 target, MdAHA8's expression, reducing levels of a specific membrane H+-ATPase. Finally, the phenotype of transgenic apple plantlets and calli demonstrated that MdCML15 modulates membrane H+-ATPase-produced rhizosphere pH lowering alongside iron homeostasis through an MdCML15-MdBT2-MdbHLH104-MdAHA8 pathway. Our results provide new insights into the relationship between Ca2+ signaling and iron homeostasis.

5.
ACS Appl Mater Interfaces ; 16(20): 25799-25812, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38727024

RESUMO

The excess production of reactive oxygen species (ROS) will delay tooth extraction socket (TES) healing. In this study, we developed an injectable thermosensitive hydrogel (NBP@BP@CS) used to treat TES healing. The hydrogel formulation incorporated black phosphorus (BP) nanoflakes, recognized for their accelerated alveolar bone regeneration and ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator aimed at enhancing angiogenesis. In vivo investigations strongly demonstrated that NBP@BP@CS improved TES healing due to antioxidation and promotion of alveolar bone regeneration by BP nanoflakes. The sustained release of NBP from the hydrogel promoted neovascularization and vascular remodeling. Our results demonstrated that the designed thermosensitive hydrogel provided great opportunity not only for ROS elimination but also for the promotion of osteogenesis and angiogenesis, reflecting the "three birds with one stone" concept, and has tremendous potential for rapid TES healing.


Assuntos
Hidrogéis , Fósforo , Extração Dentária , Cicatrização , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Fósforo/química , Alvéolo Dental/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Osteogênese/efeitos dos fármacos , Ratos , Regeneração Óssea/efeitos dos fármacos , Masculino
6.
Adv Healthc Mater ; : e2400533, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722018

RESUMO

Periodontitis, a prevalent inflammatory condition in the oral cavity, is closely associated with oxidative stress-induced tissue damage mediated by excessive reactive oxygen species (ROS) production. The jaw vascular unit (JVU), encompassing both vascular and lymphatic vessels, plays a crucial role in maintaining tissue fluid homeostasis and contributes to the pathological process in inflammatory diseases of the jaw. This study presents a novel approach for treating periodontitis through the development of an injectable thermosensitive gel (CH-BPNs-NBP). The gel formulation incorporates black phosphorus nanosheets (BPNs), which are notable for their ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator that promotes lymphatic vessel function within the JVU. These results demonstrate that the designed thermosensitive gel serve as a controlled release system, delivering BPNs and NBP to the site of inflammation. CH-BPNs-NBP not only protects macrophages and human lymphatic endothelial cells from ROS attack but also promotes M2 polarization and lymphatic function. In in vivo studies, this work observes a significant reduction in inflammation and tissue damage, accompanied by a notable promotion of alveolar bone regeneration. This research introduces a promising therapeutic strategy for periodontitis, leveraging the unique properties of BPNs and NBP within an injectable thermosensitive gel.

7.
J Ovarian Res ; 17(1): 70, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561819

RESUMO

OBJECTIVES: This retrospective study aims to evaluating the subsequent management and outcomes after first-line PARPi progression in Chinese ovarian cancer population. METHODS: Clinical and pathologic variables, treatment modalities, and outcomes were assessed. We investigated the subsequent management and outcomes after first-line PARPi progression. The objective response rate (ORR) and disease control rate (DCR) parameters were evaluated to determine the response to subsequent chemotherapy. For the survival analyses, progression-free survival 1 (PFS1), PFS2, overall survival (OS) and PFS2 - PFS1 were analysed. RESULTS: A total of 124 patients received PARPi maintenance treatment after first-line chemotherapy during the study period in our center. 44 of them (35.5%) experienced a recurrence. The median duration of PARPi in these patients was 11.1 months (range: 1.2-75.1 months). A total of 40 patients (40/44, 90.9%) received subsequent chemotherapy with 35 (35/44, 79.5%) and 5 (5/44, 11.4%) patients received platinum-based and non-platinum-based chemotherapy in our center. 2 patients (4.5%) received target therapy and other 2 patients (4.5%) received best supportive care. 27.3% (12/44) patients received secondary cytoreduction surgery (SCS). After subsequent chemotherapy, 14 patients received PARPi retreatment as maintenance therapy. In patients who received platinum-based regimens (n = 35), 23 of 35 patients (65.7%) had complete/partial response (CR/PR), 8 of 35 (22.9%) had stable disease (SD), and 4 of 35 (12.1%) had progressive disease (PD). The ORR and DCR of patients who received subsequent chemotherapy was 65.7% and 88.6%, respectively. 15 patients (57.7%, 15/26) were reported to be platinum resistant with a platinum-free interval (PFI) of < 6 months in patients whose platinum sensitivity of the second line platinum-based regimens was evaluable. Patients who received SCS after PARPi resistant associated with a borderline better PFS2 (median PFS2: 41.9 vs. 29.2 months, P = 0.051) and a non-significantly increased PFS2-PFS1 (median PFS2-PFS1: 12.2 vs. 9.8 months, P = 0.551). Patients with a PFI ≥ 12 months had a significantly better PFS2 (median PFS2: 37.0 vs. 25.3 months, P < 0.001) and a tendency towards a better PFS2-PFS1 than those with a PFI < 12 months (median PFS2-PFS1: 11.2 vs. 8.5 months, P = 0.334). A better PFS2 was observed in patients who received second PARPi maintenance therapy (median PFS2 of 35.4 vs. 28.8 months); however, the difference was not statistically significant (P = 0.200). A better PFS2-PFS1 was observed in patients who received second PARPi maintenance therapy (median PFS2-PFS1: 13.6 vs. 8.9 months, P = 0.002) than those without. CONCLUSIONS: In summary, some degree of resistance to standard subsequent platinum and non-platinum chemotherapy is noted in the entire cohort. A trend towards higher benefit from subsequent chemotherapy after first-line PARP inhibitors progression was observed in the PFI ≥ 12 months subgroup than those with PFI < 12 months. PARPi retreatment as maintenance therapy and SCS can be offered to some patients with PARPi resistance.


Assuntos
Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Feminino , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Estudos Retrospectivos , Neoplasias Ovarianas/patologia , Intervalo Livre de Progressão , Análise de Sobrevida , Platina/farmacologia , Platina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico
8.
Science ; 384(6692): 185-189, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38603510

RESUMO

Ultrahigh-power-density multilayer ceramic capacitors (MLCCs) are critical components in electrical and electronic systems. However, the realization of a high energy density combined with a high efficiency is a major challenge for practical applications. We propose a high-entropy design in barium titanate (BaTiO3)-based lead-free MLCCs with polymorphic relaxor phase. This strategy effectively minimizes hysteresis loss by lowering the domain-switching barriers and enhances the breakdown strength by the high atomic disorder with lattice distortion and grain refining. Benefiting from the synergistic effects, we achieved a high energy density of 20.8 joules per cubic centimeter with an ultrahigh efficiency of 97.5% in the MLCCs. This approach should be universally applicable to designing high-performance dielectrics for energy storage and other related functionalities.

9.
Adv Sci (Weinh) ; : e2402272, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639395

RESUMO

Here, a photocatalytic asymmetric multicomponent cascade Minisci reaction of ß-carbolines with enamides and diazo compounds is reported, enabling an effective enantioselective radical C─H functionalization of ß-carbolines with high yields and enantioselectivity (up to 83% yield and 95% ee). This enantioselective multicomponent Minisci protocol exhibits step economy, high chemo-/enantio-selective control, and good functional group tolerance, allowing access to a variety of valuable chiral ß-carbolines. Notably, diazo compounds are suitable radical precursors in enantioselective cascade radical reactions. Moreover, the efficiency and practicality of this approach are demonstrated by the asymmetric synthesis of bioactive compounds and natural products.

10.
World J Gastroenterol ; 30(13): 1911-1925, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38659485

RESUMO

BACKGROUND: Liuweiwuling Tablet (LWWL) is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus (HBV) infection. Previous studies have indicated an anti-HBV effect of LWWL, specifically in terms of antigen inhibition, but the underlying mechanism remains unclear. AIM: To investigate the potential mechanism of action of LWWL against HBV. METHODS: In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines. The in vivo experiment involved a hydrodynamic injection-mediated mouse model with HBV replication. Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL. RESULTS: In HepG2.1403F cells, LWWL (0.8 mg/mL) exhibited inhibitory effects on HBV DNA, hepatitis B surface antigen and pregenomic RNA (pgRNA) at rates of 51.36%, 24.74% and 50.74%, respectively. The inhibition rates of LWWL (0.8 mg/mL) on pgRNA/covalently closed circular DNA in HepG2.1403F, HepG2.2.15 and HepG2.A64 cells were 47.78%, 39.51% and 46.74%, respectively. Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis (PI3K-AKT, CASP8-CASP3 and P53 pathways). Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group (CG) among HBV-replicating cell lines, including HepG2.2.15 (2.92% ± 1.01% vs 6.68% ± 2.04%, P < 0.05), HepG2.A64 (4.89% ± 1.28% vs 8.52% ± 0.50%, P < 0.05) and HepG2.1403F (3.76% ± 1.40% vs 7.57% ± 1.35%, P < 0.05) (CG vs LWWL-treated group). However, there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells (5.04% ± 0.74% vs 5.51% ± 1.57%, P > 0.05), L02 cells (5.49% ± 0.80% vs 5.48% ± 1.01%, P > 0.05) and LX2 cells (6.29% ± 1.54% vs 6.29% ± 0.88%, P > 0.05). TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBV-replicating mouse model, while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model. CONCLUSION: Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV, potentially involving selective regulation of apoptosis. These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.


Assuntos
Antivirais , Apoptose , DNA Viral , Medicamentos de Ervas Chinesas , Vírus da Hepatite B , Comprimidos , Replicação Viral , Apoptose/efeitos dos fármacos , Animais , Humanos , Vírus da Hepatite B/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Células Hep G2 , Antivirais/farmacologia , Replicação Viral/efeitos dos fármacos , Modelos Animais de Doenças , Antígenos de Superfície da Hepatite B/metabolismo , Masculino , Hepatite B/tratamento farmacológico , Hepatite B/virologia , RNA Viral/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/virologia
11.
Int J Gen Med ; 17: 1533-1543, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38680194

RESUMO

Purpose: The association between serum uric acid (SUA) and atrial fibrillation (AF) has been widely focused on and studied in recent years. However, the exact association between SUA and AF is unclear, and the effect of gender on the association between SUA levels and AF has been controversial. This study aimed to investigate the association between SUA levels and non-valvular AF (NVAF) and the potential effect of gender on it. Patients and Methods: A total of 866 NVAF patients (463 males, age 69.44 ± 8.07 years) and 646 sex-matched control patients in sinus rhythm, with no history of arrhythmia were included in this study. t-test, ANOVA, and chi-square test were used for baseline data analysis. The receiver operating characteristic curve, logistic regression and Pearson correlation analysis were used for correlation analysis. Results: Compared to controls, NVAF patients exhibited higher SUA (P<0.001). After adjusting for confounders of NVAF, SUA remained significantly associated with NVAF, regardless of gender (OR= 1.31, 95% CI 1.18-1.43, P<0.001). SUA demonstrated higher predictability and sensitivity in predicting the occurrence of female NVAF compared to male (area under the curve was 0.68 (95% CI 0.64-0.72, P<0.001), sensitivity 87.3%), with the optimal cut-off point identified as 5.72 mg/dL. Furthermore, SUA levels correlated with APOA1, Scr and NT-proBNP in NVAF patients. SUA levels varied significantly among NVAF subtypes. Conclusion: High SUA levels were independently associated with NVAF, regardless of gender. SUA exhibited higher predictability and sensitivity in predicting the occurrence of NVAF in females compared to males. High SUA levels may affect other NVAF-related factors and participate in the pathophysiological process of NVAF.

12.
Medicine (Baltimore) ; 103(14): e37706, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579031

RESUMO

RATIONALE: Kaposiform hemangioendothelioma is an aggressive vascular tumor that is often associated with life-threatening coagulopathies and Kasabach-Merritt phenomenon. Pathologic biopsies can provide a good basis for diagnosis and treatment. Therapy with srolimus combined with glucocorticoids may offer patients a favorable prognosis. PATIENT CONCERNS: A large purplish-red mass on the knee of a child with extremely progressive thrombocytopenia and refractory coagulation abnormalities. Conventional doses of glucocorticoids alone failed to improve coagulation abnormalities and the child developed large cutaneous petechiae and scalp hematomas. DIAGNOSIS: Kaposiform hemangioendothelioma combined with Kasabach-Merritt phenomenon. INTERVENTIONS: The patient received prednisolone 2.0 mg/kg*d for 4 days. Blood products were transfused to ensure vital signs and to complete the pathologic biopsy. Sirolimus combined with prednisolone was given after clarifying the diagnosis of Kaposiform hemangioendothelioma. OUTCOMES: The tumor basically disappeared on examination and the ultrasound showed a subcutaneous hyperechoic mass with normal blood flow. LESSONS: Sirolimus combined with glucocorticoids is effective in controlling Kasabach-Merritt phenomenon and pathologic biopsy is important for definitive diagnosis.


Assuntos
Transtornos da Coagulação Sanguínea , Hemangioendotelioma , Síndrome de Kasabach-Merritt , Sarcoma de Kaposi , Humanos , Recém-Nascido , Transtornos da Coagulação Sanguínea/complicações , Glucocorticoides/uso terapêutico , Hemangioendotelioma/complicações , Hemangioendotelioma/tratamento farmacológico , Hemangioendotelioma/diagnóstico , Síndrome de Kasabach-Merritt/tratamento farmacológico , Prednisolona/uso terapêutico , Sarcoma de Kaposi/patologia , Sirolimo/uso terapêutico
13.
World J Surg Oncol ; 22(1): 104, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637834

RESUMO

OBJECTIVES: To investigate the clinicopathological characteristics and prognosis of patients with primary sarcoma of the uterine cervix. METHODS: We identified all patients with primary cervical sarcomas treated at our institution from 2002 to 2020 and analyzed the clinicopathological characteristics and prognosis. RESULTS: 34 patients were identified, 7 (20.6%) patients had leiomyosarcoma, 6 (17.6%) had carcinosarcoma, 5 (14.7%) had Ewing sarcoma, 4 (11.8%) had rhabdomyosarcoma, 4 (11.8%) had undifferentiated sarcoma, 2 (5.9%) had adenosarcoma, 2 (5.9%) had endometrial stromal sarcoma, 1 (2.9%) had dermatofibrosarcoma protuberans, 1 (2.9%) had alveolar soft tissue sarcoma and 2 (5.9%) had sarcoma not otherwise specified. The median age of the whole patients was 43.5 years (range, 13-63). The median age of patients with Ewing sarcoma or rhabdomyosarcoma was 22 years (range, 13-39) and 17 years (range, 13-36 years), respectively. The distribution by stage was: stage I in 21 (61.8%) patients, stage II in 4 (11.8%), stage III in 6 (17.6%) and stage IV in 3 (8.8%). Overall, 30 patients (88.2%) received surgical treatment. The median follow-up was 33.3 months (range 3.6-187.3 months). 11 patients died within 2 years after diagnosis, most of them were patients with carcinosarcoma or undifferentiated sarcoma (45.5%, 5/11). In the entire cohort, 2- and 5-year OS were 67.2% and 56.9%, respectively. 5-year OS was 25.0% for undifferentiated sarcoma, 50.0% for rhabdomyosarcoma, 50.0% for carcinosarcoma, 53.3% for Ewing sarcoma, 57.1% for leiomyosarcoma. CONCLUSION: Cervical sarcomas are rare neoplasms with multiple histological subtypes and follow an aggressive course. Prognosis may be associated with tumor histology and stage.


Assuntos
Carcinossarcoma , Leiomiossarcoma , Rabdomiossarcoma , Sarcoma de Ewing , Sarcoma , Neoplasias do Colo do Útero , Neoplasias Uterinas , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Leiomiossarcoma/patologia , Sarcoma de Ewing/cirurgia , Neoplasias do Colo do Útero/cirurgia , Neoplasias Uterinas/diagnóstico , Sarcoma/cirurgia , Sarcoma/diagnóstico , Carcinossarcoma/patologia , Rabdomiossarcoma/cirurgia , Prognóstico
14.
J Bacteriol ; 206(5): e0000324, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38606980

RESUMO

In most actinomycetes, GlnR governs both nitrogen and non-nitrogen metabolisms (e.g., carbon, phosphate, and secondary metabolisms). Although GlnR has been recognized as a global regulator, its regulatory role in central carbon metabolism [e.g., glycolysis, gluconeogenesis, and the tricarboxylic acid (TCA) cycle] is largely unknown. In this study, we characterized GlnR as a direct transcriptional repressor of the pckA gene that encodes phosphoenolpyruvate carboxykinase, catalyzing the conversion of the TCA cycle intermediate oxaloacetate to phosphoenolpyruvate, a key step in gluconeogenesis. Through the transcriptomic and quantitative real-time PCR analyses, we first showed that the pckA transcription was upregulated in the glnR null mutant of Amycolatopsis mediterranei. Next, we proved that the pckA gene was essential for A. mediterranei gluconeogenesis when the TCA cycle intermediate was used as a sole carbon source. Furthermore, with the employment of the electrophoretic mobility shift assay and DNase I footprinting assay, we revealed that GlnR was able to specifically bind to the pckA promoter region from both A. mediterranei and two other representative actinomycetes (Streptomyces coelicolor and Mycobacterium smegmatis). Therefore, our data suggest that GlnR may repress pckA transcription in actinomycetes, which highlights the global regulatory role of GlnR in both nitrogen and central carbon metabolisms in response to environmental nutrient stresses. IMPORTANCE: The GlnR regulator of actinomycetes controls nitrogen metabolism genes and many other genes involved in carbon, phosphate, and secondary metabolisms. Currently, the known GlnR-regulated genes in carbon metabolism are involved in the transport of carbon sources, the assimilation of short-chain fatty acid, and the 2-methylcitrate cycle, although little is known about the relationship between GlnR and the TCA cycle and gluconeogenesis. Here, based on the biochemical and genetic results, we identified GlnR as a direct transcriptional repressor of pckA, the gene that encodes phosphoenolpyruvate carboxykinase, a key enzyme for gluconeogenesis, thus highlighting that GlnR plays a central and complex role for dynamic orchestration of cellular carbon, nitrogen, and phosphate fluxes and bioactive secondary metabolites in actinomycetes to adapt to changing surroundings.


Assuntos
Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Gluconeogênese , Nitrogênio , Gluconeogênese/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Nitrogênio/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Amycolatopsis/metabolismo , Amycolatopsis/genética , Regiões Promotoras Genéticas , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Fosfoenolpiruvato Carboxiquinase (ATP)/genética , Ciclo do Ácido Cítrico/genética , Actinobacteria/genética , Actinobacteria/metabolismo
15.
New Phytol ; 242(6): 2555-2569, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38594216

RESUMO

Gibberellic acid (GA) plays a central role in many plant developmental processes and is crucial for crop improvement. DELLA proteins, the core suppressors in the GA signaling pathway, are degraded by GA via the 26S proteasomal pathway to release the GA response. However, little is known about the phosphorylation-mediated regulation of DELLA proteins. In this study, we combined GA response assays with protein-protein interaction analysis to infer the connection between Arabidopsis thaliana DELLAs and the C-TERMINAL DOMAIN PHOSPHATASE-LIKE 3 (CPL3), a phosphatase involved in the dephosphorylation of RNA polymerase II. We show that CPL3 directly interacts with DELLA proteins and promotes DELLA protein stability by inhibiting its degradation by the 26S proteasome. Consequently, CPL3 negatively modulates multiple GA-mediated processes of plant development, including hypocotyl elongation, flowering time, and anthocyanin accumulation. Taken together, our findings demonstrate that CPL3 serves as a novel regulator that could improve DELLA stability and thereby participate in GA signaling transduction.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Flores , Regulação da Expressão Gênica de Plantas , Giberelinas , Ligação Proteica , Giberelinas/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Flores/crescimento & desenvolvimento , Flores/genética , Proteólise , Estabilidade Proteica , Fosfoproteínas Fosfatases/metabolismo , Fosfoproteínas Fosfatases/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/metabolismo , Transdução de Sinais , Antocianinas/metabolismo , Fosforilação
16.
Langmuir ; 40(17): 9134-9143, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38636482

RESUMO

Wound healing has been a persistent clinical challenge for a long time. Electrical stimulation is an effective therapy with the potential to accelerate wound healing. In this work, the self-powered electrospun nanofiber membranes (triples) were constructed as multifunctional wound dressings with electrical stimulation and biochemical capabilities. Triple was composed of a hydrolyzable inner layer with antiseptic and hemostatic chitosan, a hydrophilic core layer loaded with conductive AgNWs, and a hydrophobic outer layer fabricated by self-powered PVDF. Triple exhibited presentable wettability and acceptable moisture permeability. Electrical performance tests indicated that triple can transmit electrical signals formed by the piezoelectric effect to the wound. High antibacterial activities were observed for triple against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, with inhibition rates of 96.52, 98.63, and 97.26%, respectively. In vitro cell assays demonstrated that triple cells showed satisfactory proliferation and mobility. A whole blood clotting test showed that triple can enhance hemostasis. The innovative self-powered multifunctional fibers presented in this work offer a promising approach to addressing complications and expediting the promotion of chronic wound healing.


Assuntos
Antibacterianos , Escherichia coli , Nanofibras , Pseudomonas aeruginosa , Staphylococcus aureus , Cicatrização , Cicatrização/efeitos dos fármacos , Nanofibras/química , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Quitosana/química , Humanos , Animais , Proliferação de Células/efeitos dos fármacos
17.
J Hazard Mater ; 470: 134114, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38547755

RESUMO

Volatile organic compounds (VOCs) cause severe environmental pollution and are potentially toxic to humans who have no defense against exposure. Catalytic oxidation of these compounds has thus become an interesting research topic. In this study, microcrystalline CeMnO3 catalysts were prepared by a precipitant-concentration-induced strategy and evaluated for the catalytic oxidation of toluene/benzene. The effect of crystal size on catalytic performance was confirmed by XRD, TEM, N2 adsorption-desorption, XPS, Raman, H2-TPR, and TPSR. The CeMnO3 catalyst with more Mn3+-Ov-Ce4+ active sites exhibited enhanced VOCs catalytic oxidation performance, lowest active energy, and highest turnover frequency, which was attributed to its larger surface area, lower crystal size, higher low-temperature reducibility, and presence of more oxygen defects. In-situ FTIR results suggested more oxygen vacancies can profoundly promote the conversion of benzoate to maleate species, the rate-determining step of toluene oxidation. The work provides a convenient and efficient strategy to prepare single-metal or multi-metal oxide catalysts with smaller crystal sizes for VOC oxidation or other oxidation reactions.

18.
Adv Mater ; : e2400648, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488330

RESUMO

The increasingly severe plastic pollution has urged an inevitable trend to develop biodegradable plastic products that can take over synthetic plastics. As one of the most abundant natural polymers, polysaccharides are an ideal candidate to substitute synthetic plastics. The rigidity of polysaccharide chains principally allows for high strength and stiffness of their materials, however, challenges the facile orientation in material processing. Here, a general hydrogen bond-mediated plasticization strategy to regulate isotropic sodium alginate (SA) chains to a highly ordered state is developed, and alginate plastics with high performances are fabricated. It is revealed that hydroxyl groups in glycerol modulate the viscoelasticity of SA solids by forming strong hydrogen bonds with SA chains, achieving a large stretchability at a high solid content. Highly orientated alginate films exhibit a superior tensile strength of 575 MPa and toughness of 60.7 MJ m-3, outperforming most regenerated biomass films. The high solid content and large stretchability mediated by strong hydrogen bonding ensure plastic molding of solid-like SA with high fidelity. This hydrogen bond-mediated plasticity provides a facile but effective method to justify the high performances of polysaccharide-based plastics.

19.
Sci China Life Sci ; 67(5): 1010-1026, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38489007

RESUMO

Alveolar bone regeneration has been strongly linked to macrophage polarization. M1 macrophages aggravate alveolar bone loss, whereas M2 macrophages reverse this process. Berberine (BBR), a natural alkaloid isolated and refined from Chinese medicinal plants, has shown therapeutic effects in treating metabolic disorders. In this study, we first discovered that culture supernatant (CS) collected from BBR-treated human bone marrow mesenchymal stem cells (HBMSCs) ameliorated periodontal alveolar bone loss. CS from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in vitro. To clarify the underlying mechanism, the bioactive materials were applied to different animal models. We discovered macrophage colony-stimulating factor (M-CSF), which regulates macrophage polarization and promotes bone formation, a key macromolecule in the CS. Injection of pure M-CSF attenuated experimental periodontal alveolar bone loss in rats. Colony-stimulating factor 1 receptor (CSF1R) inhibitor or anti-human M-CSF (M-CSF neutralizing antibody, Nab) abolished the therapeutic effects of the CS of BBR-treated HBMSCs. Moreover, AKT phosphorylation in macrophages was activated by the CS, and the AKT activator reversed the negative effect of the CSF1R inhibitor or Nab. These results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT axis. Further studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction sockets. Overall, our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.


Assuntos
Perda do Osso Alveolar , Berberina , Regeneração Óssea , Fator Estimulador de Colônias de Macrófagos , Macrófagos , Células-Tronco Mesenquimais , Berberina/farmacologia , Humanos , Animais , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Regeneração Óssea/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Ratos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Perda do Osso Alveolar/metabolismo , Masculino , Ratos Sprague-Dawley , Osteogênese/efeitos dos fármacos , Células Cultivadas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos
20.
Curr Med Chem ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468516

RESUMO

Afterglow materials with organic room temperature phosphorescence (RTP) or thermally activated delayed fluorescence (TADF) exhibit significant potential in biological imaging due to their long lifetime. By utilizing time-resolved technology, interference from biological tissue fluorescence can be mitigated, enabling high signal-- to-background ratio imaging. Despite the continued emergence of individual reports on RTP or TADF in recent years, comprehensive reviews addressing these two materials are rare. Therefore, this review aims to provide a comprehensive overview of several typical molecular designs for organic RTP and TADF materials. It also explores the primary methods through which triplet excitons resist quenching by water and oxygen. Furthermore, we analyze the principal challenges faced by afterglow materials and discuss key directions for future research with the hope of inspiring developments in afterglow imaging.

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