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Chemotherapy-induced liver injury (CILI) is a pressing concern in cancer patients. One promising approach involves activating nuclear factor erythroid 2-related factor 2 (Nrf2) to mitigate CILI. However, selectively activating liver Nrf2 without compromising chemotherapy's efficacy has remained elusive. Herein, two RNAi delivery strategies were explored: lipid nanoparticle (LNP) and N-acetylgalactosamine (GalNAc) delivery systems loaded with siRNA designed to silence Kelch-like-ECH associated protein 1 (Keap1) by aiming for liver-specific Nrf2 activation. Remarkably, siKeap1-LNP exhibited unintended tumor targeting alongside liver effects, thereby potentially promoting tumor progression. Conversely, siKeap1-GalNAc did not compromise chemotherapy efficacy and outperformed the conventional Nrf2 activator, bardoxolone, in mitigating CILI. This study proposes siKeap1-GalNAc as a promising therapeutic avenue for liver injury. Importantly, our study bridges a crucial gap concerning the delivery system for liver targeting but not tumor targeting and underscores the importance of selecting nucleic acid delivery systems tailored to specific diseases, not just to specific organs.
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Antineoplásicos , Hepatopatias , Neoplasias , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias/terapia , Antineoplásicos/uso terapêuticoRESUMO
The heteroanionic materials (HAMs) have attracted more and more attention because they can better balance the functional properties of materials. However, their rational structural design is still a great challenge. Here, by using the antiperovskite Ba3S[GeS4] as a template and calculating the tolerance factor (t) as a reference, eight heteroanionic oxychalcogenides with balanced properties were finally synthesized by a partially group-substitution method. Among them, Ba3[CO3][MQ4] (M = Ge, Sn; Q = S, Se) are centrosymmetric (CS) crystals and realize optimization of band gaps and birefringence. For Ae3[TO3][SnOQ3] (Ae = Sr, Ba; T = Si, Ge; Q = S, Se), thanks to the novel [TO4SnQ3] polyanionic groups for the regulation to the antiperovskite structures and the contributions to the nonlinear optical (NLO) properties, they achieve the structural transition from CS to noncentrosymmetry and accomplish an excellent balance among the critical performance parameters as the potential candidates for the infrared NLO materials, including phase-matchable behavior, wide band gaps (Eg = 3.26-3.95 eV), high laser damage threshold (LDT = 3.2-4.4 × AgGaS2), suitable birefringence (Δn = 0.065-0.098@2090 nm) and sufficiently strong second-harmonic generation responses (about 0.6-0.9 × AgGaS2). Moreover, benefiting from crystallization in the polar space groups, they exhibit ferroelectricity and piezoelectricity at room temperature. As far as we know, this is the first reported fully inorganic antiperovskite ferroelectric. These demonstrate that our strategy is desirable and can provide some unique insights into the development of HAMs or antiperovskite materials with specific functions or structures.
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STUDY QUESTION: What is the effect of small follicles on clinical pregnancy and multiple pregnancy rates in women undergoing IUI with ovarian stimulation (IUI-OS)? SUMMARY ANSWER: The presence of ≥2 small follicles with a diameter of 10-12 or 12-14 mm was associated with an increased chance of clinical pregnancy and the presence of any 12-14 mm or larger follicles, but not smaller follicles, was statistically significantly associated with an increased risk for multiple pregnancy. WHAT IS KNOWN ALREADY: IUI-OS is widely used as the first-line treatment for unexplained or mild male factor infertility. However, IUI is associated with the risk of multiple pregnancy. While the positive association between the number of follicles ≥14 mm and the chance of pregnancy and the risk of multiple pregnancy is known, the impact of smaller follicles is uncertain. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study that included women undergoing IUI cycles from January 2007 to May 2021 in one assisted reproduction center. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied the impact of the number and size of follicles on trigger day on clinical pregnancy and multiple pregnancy rates. Generalized estimation equation regression models were used to compute unadjusted and adjusted odds ratios and 95% CI in all women and only women who achieved clinical pregnancy separately. The chance of clinical pregnancy and multiple pregnancy for different numbers of small follicles in cycles with one >18-mm follicle was calculated using marginal effects estimate. MAIN RESULTS AND THE ROLE OF CHANCE: This cohort included 12 933 IUI cycles in 7504 women. The overall clinical pregnancy rate was 16.1% (2081/12 933), with a multiple pregnancy rate of 10.5% (218/2081). In the adjusted analysis, the chance of clinical pregnancy increased significantly with the increase in the number of follicles with the diameter of 14-16, 16-18, and 18-20 mm. As for 10-12 mm [adjusted odds ratio (aOR) 1.22, 95% CI 1.02-1.46] and 12-14 mm (aOR 1.29, 95% CI 1.07-1.56) follicles, only groups with ≥2 follicles of those sizes showed significantly increased chance of clinical pregnancy. In cycles that led to pregnancy, follicles with the diameter of 12-14 mm were associated with an increased risk of multiple pregnancy (aOR 1.73, 95% CI 1.19-2.53 for one such follicle; aOR 2.27, 95% CI 1.44-3.56 for ≥2 such follicles), while 10- to 12-mm follicles were not significantly associated with multiple pregnancy (aOR 1.18, 95% CI 0.72-1.95 for ≥2 such follicles). The associations of multiple pregnancy were similar when including all cycles. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective observational study from a single center. The records of follicle diameter in our center were of a 2-mm interval which limited our ability to analyze the size of follicle as a continuous variable. Also, the number of cycles with a high number of small follicles was still limited which impeded more detailed analysis on the ≥2 follicles subgroup. Similarly, the value of some parts of the marginal probability estimation for multiple pregnancy versus pregnancy according to size and number of follicles was also limited by the low sample size of certain combinations. WIDER IMPLICATIONS OF THE FINDINGS: Follicles larger than 10 mm, especially those ≥12 mm, may need to be clearly recorded during transvaginal ultrasound surveillance and their potential effects on both pregnancy and multiple pregnancy can be discussed with couples undergoing IUI. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (Grant numbers 82201912, 82371651, and 82071615) and Shanghai Sailing Program (21YF1423200). B.W.M. is supported by an NHMRC Investigator grant (GNT1176437). B.W.M. reports consultancy for ObsEva and Merck and travel support from Merck. B.W.M. has received research funding from Ferring and Merck. The authors declare no other competing interests. TRIAL REGISTRATION NUMBER: N/A.
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Infertilidade Masculina , Gravidez , Masculino , Humanos , Feminino , Taxa de Gravidez , Estudos de Coortes , Estudos Retrospectivos , China , Infertilidade Masculina/terapia , Gravidez Múltipla , Inseminação , Indução da Ovulação/métodosRESUMO
The management of hypertrophic scars (HSs), characterized by excessive collagen production, involves various nonsurgical and surgical interventions. However, the absence of a well-defined molecular mechanism governing hypertrophic scarring has led to less-than-ideal results in clinical antifibrotic treatments. Therefore, our study focused on the role of decorin (DCN) and its regulatory role in the TGF-ß/Smad signalling pathway in the development of HSs. In our research, we observed a decrease in DCN expression within hypertrophic scar tissue and its derived cells (HSFc) compared to that in normal tissue. Then, the inhibitory effect of DCN on collagen synthesis was confirmed in Fc and HSFc via the detection of fibrosis markers such as COL-1 and COL-3 after the overexpression and knockdown of DCN. Moreover, functional assessments revealed that DCN suppresses the proliferation, migration and invasion of HSFc. We discovered that DCN significantly inhibits the TGF-ß1/Smad3 pathway by suppressing TGF-ß1 expression, as well as the formation and phosphorylation of Smad3. This finding suggested that DCN regulates the synthesis of collagen-based extracellular matrix and fibrosis through the TGF-ß1/Smad3 pathway.
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Cicatriz Hipertrófica , Decorina , Proteína Smad3 , Fator de Crescimento Transformador beta , Decorina/genética , Decorina/metabolismo , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patologia , Fator de Crescimento Transformador beta/metabolismo , Transdução de Sinais , Técnicas de Silenciamento de Genes , Humanos , Proteína Smad3/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Matriz Extracelular/metabolismo , Proliferação de Células , Movimento CelularRESUMO
BACKGROUND: Acute Kidney Injury (AKI), a prevalent complication of Liver Transplantation (LT) that occurs during the perioperative period has been established to profoundly impact the prognosis of transplant recipients. This study aimed to investigate the mechanism of the hepatic IRI-induced AKI and to identify potential therapeutic targets for treating this condition and improving the prognosis of LT patients. METHODS: An integrated transcriptomics and proteomics approach was employed to investigate transcriptional and proteomic alterations in hepatic IRI-induced AKI and the hypoxia-reoxygenation (H/R) model using TCMK-1 cells and the hepatic IRI-induced AKI mouse model using male C57BL/6 J mice were employed to elucidate the underlying mechanisms. Hematoxylin-eosin staining, reverse transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot were used to assess the effect of Rosiglitazone (RGZ) on hepatic IRI-induced AKI in vitro and in vivo. RESULTS: According to the results, 322 genes and 128 proteins were differentially expressed between the sham and AKI groups. Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway analyses revealed significant enrichment in pathways related to amino acid and lipid metabolism. Additionally, the Protein-Protein Interaction (PPI) network analysis of the kidney tissues obtained from a hepatic IRI-induced AKI mouse model highlighted arachidonic acid metabolism as the most prominent pathway. Animal and cellular analyses further revealed that RGZ, a PPAR-γ agonist, could inhibit the expression of the PPAR-γ/NF-κB signaling pathway-associated proteins in in vitro and in vivo. CONCLUSIONS: These findings collectively suggest that RGZ ameliorates hepatic IRI-induced AKI via PPAR-γ/NF-κB signaling pathway modulation, highlighting PPAR-γ as a crucial therapeutic target for AKI prevention post-LT.
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Injúria Renal Aguda , Ácido Araquidônico , Fígado , Camundongos Endogâmicos C57BL , NF-kappa B , PPAR gama , Traumatismo por Reperfusão , Rosiglitazona , Transdução de Sinais , Animais , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Masculino , Rosiglitazona/farmacologia , Rosiglitazona/uso terapêutico , PPAR gama/metabolismo , NF-kappa B/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Ácido Araquidônico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Camundongos , Linhagem Celular , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Mapas de Interação de ProteínasRESUMO
Chemotherapy-induced diarrhea causes dehydration, debilitation, infection, and even death, but there are currently no Food and Drug Administration (FDA)-approved drugs for treatment of chemotherapy-induced diarrhea. It is generally believed that the timely regulation of intestinal stem cell (ISC) fate may provide a meaningful solution for intestinal injuries. However, the lineage plasticity of ISCs during and after chemotherapy remains poorly understood. Here, we demonstrated that palbociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, regulated the fate of active or quiescent ISCs, provided multilineage protection from the toxicity of several different chemotherapeutics, and accelerated gastrointestinal epithelium recovery. Consistent with in vivo results, we determined that palbociclib enhanced intestinal organoid and ex vivo tissue survival after chemotherapy. Lineage tracing studies have shown that palbociclib protects active ISCs marked by Lgr5 and Olfm4 during chemotherapy and unexpectedly activates quiescent ISCs marked by Bmi1 to immediately participate in crypt regeneration after chemotherapy. Furthermore, palbociclib does not decrease the efficacy of cytotoxic chemotherapy in tumor grafts. The experimental evidence suggests that the combination of CDK4/6 inhibitors with chemotherapy could reduce damage to the gastrointestinal epithelium in patients. © 2023 The Pathological Society of Great Britain and Ireland.
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Antineoplásicos , Diarreia , Humanos , Diarreia/patologia , Diferenciação Celular , Células-Tronco/patologia , Reino Unido , Mucosa Intestinal/patologia , Quinase 4 Dependente de CiclinaRESUMO
OBJECTIVES: To explore the influencing factors and relationships associated with decisional conflict of dialysis modality in End-stage kidney disease (ESKD) patients. METHODS: This study was a survey-based cross-sectional investigation conducted on 150 ESKD patients in a third-class hospital in Wuhan. The general information questionnaire, decisional conflict scale, Montreal cognitive assessment, frail scale, perceived social support scale, and brief health literacy screen were used for investigation. SPSS 25.0 was used to compare the differences between the decisional and non-decisional conflict groups, and AMOS 23.0 was used to construct a structural equation model to explore the influencing factors. RESULTS: The incidence of decisional conflict in 150 ESKD patients was 33.3% (50/150). Binary logistic regression analysis showed that the independent risk factors for decisional conflict of dialysis modality in ESKD patients included monthly household income (OR = 0.184), cognitive function (OR = 7.0), social support (OR = 0.891), health literacy (OR = 0.608), the level of eGFR (OR = 1.488), and the level of cTnI (OR = 9.558). The constructed path analysis model had a good fit (x2/df = 1.499, GFI = 0.957, AGFI = 0.911, NFI = 0.906, CFI = 0.967, RMSEA = 0.055). The path analysis showed that health literacy (0.577) had the greatest impact on the decisional conflict, with a direct effect of 0.480 and an indirect effect of 0.097 through cognitive function and monthly household income. Next was social support, with an effect value of 0.434. CONCLUSIONS: In clinical practice, it is important to enhance the health literacy of patients and their families and to provide advanced education on dialysis plans. Additionally, in managing and planning chronic kidney disease progression and dialysis, it is recommended to regularly and systematically assess cognitive function, particularly before the patient's cognitive impairment worsens or the severity of the disease progresses. Advanced care planning can be established through collaboration between healthcare professionals and patients to ensure appropriate decision-making and management. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: This paper finds that the factors that influence and relate to dialysis methods in end-stage renal disease patients help nurses exercise autonomy better, assist patients in reducing their decisional conflict, and improve clinical outcomes. PATIENT OR PUBLIC CONTRIBUTION: Patients received a relevant questionnaire survey, and caregivers assisted in conducting the study.
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Conflito Psicológico , Letramento em Saúde , Falência Renal Crônica , Diálise Renal , Apoio Social , Humanos , Falência Renal Crônica/terapia , Falência Renal Crônica/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Diálise Renal/psicologia , China/epidemiologia , Estudos Transversais , Tomada de Decisões , Idoso , Análise de Classes Latentes , Adulto , Taxa de Filtração GlomerularRESUMO
BACKGROUND: Many studies have focused on the quality of pain management in hospitalized patients with cancer pain, while what happens after discharge remains unclear. AIM: The purpose of this study was to investigate the pain intensity and satisfaction of pain relief among a large sample of Chinese patients with cancer pain after discharge. DESIGN: Cross-sectional, descriptive, correlational research. SETTINGS AND SAMPLE: ABOUT: 1,013 patients were recruited in a tertiary cancer hospital, and their residence addresses were distributed in 6 geographical regions, including 26 provinces, municipalities, and autonomous regions. METHODS: The 1,013 patients with cancer pain were discharged from the wards of a national cancer hospital in China from July 2020 to October 2021. A nurse in the pain clinic followed the patients based on a whole-process information system and collected the data after the cancer pain patients were discharged. The study methods followed the STROBE guidelines. RESULTS: The average age of 1,013 discharged patients was 61.30 (±12.56) years. Moderate and severe background pain (BGP) was reported in 749 patients (73.94%), and more than 3 instances of breakthrough pain (BTP) in the past 24 hours were reported in 541 patients (53.41%). More severe BGP was associated with more frequent BTP (p < .01). In addition, there were 572 patients (56.47%) whose satisfaction with pain relief was lower than 70%. More severe BGP was associated with a lower satisfaction degree (r = -0.796, p < .01). CONCLUSIONS: Pain among discharged Chinese patients with cancer is poorly managed, and there is a low degree of satisfaction with pain relief. Nurses can do more work to assist cancer patients in managing pain more effectively by ensuring they have a plan to report and manage pain after discharge.
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Dor do Câncer , Manejo da Dor , Medição da Dor , Alta do Paciente , Satisfação do Paciente , Humanos , Feminino , Masculino , China , Pessoa de Meia-Idade , Estudos Transversais , Manejo da Dor/métodos , Manejo da Dor/normas , Manejo da Dor/estatística & dados numéricos , Idoso , Satisfação do Paciente/estatística & dados numéricos , Dor do Câncer/psicologia , Dor do Câncer/terapia , Alta do Paciente/estatística & dados numéricos , Alta do Paciente/normas , Medição da Dor/métodos , Medição da Dor/estatística & dados numéricos , Adulto , Neoplasias/complicações , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Hand-foot syndrome (HFS) is a serious dose-limiting cutaneous toxicity of capecitabine-containing chemotherapy, leading to a deteriorated quality of life and negative impacts on chemotherapy treatment. The symptoms of HFS have been widely reported, but the precise molecular and cellular mechanisms remain unknown. The metabolic enzyme of capecitabine, thymidine phosphorylase (TP) may be related to HFS. Here, we investigated whether TP contributes to the HFS and the molecular basis of cellular toxicity of capecitabine. METHODS: TP-/- mice were generated to assess the relevance of TP and HFS. Cellular toxicity and signalling mechanisms were assessed by in vitro and in vivo experiments. RESULTS: TP-/- significantly reduced capecitabine-induced HFS, indicating that the activity of TP plays a critical role in the development of HFS. Further investigations into the cellular mechanisms revealed that the cytotoxicity of the active metabolite of capecitabine, 5-DFUR, was attributed to the cleavage of GSDME-mediated pyroptosis. Finally, we demonstrated that capecitabine-induced HFS could be reversed by local application of the TP inhibitor tipiracil. CONCLUSION: Our findings reveal that the presence of elevated TP expression in the palm and sole aggravates local cell cytotoxicity, further explaining the molecular basis underlying 5-DFUR-induced cellular toxicity and providing a promising approach to the therapeutic management of HFS.
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Fluoruracila , Síndrome Mão-Pé , Animais , Camundongos , Capecitabina/farmacologia , Fluoruracila/farmacologia , Síndrome Mão-Pé/tratamento farmacológico , Síndrome Mão-Pé/etiologia , Piroptose , Timidina Fosforilase/genética , Timidina Fosforilase/metabolismo , Qualidade de Vida , Desoxicitidina/efeitos adversosRESUMO
The electrocatalytic CO2 reduction reaction (CO2 RR) is an attractive technology for CO2 valorization and high-density electrical energy storage. Achieving a high selectivity to C2+ products, especially ethylene, during CO2 RR at high current densities (>500 mA cm-2 ) is a prized goal of current research, though remains technically very challenging. Herein, it is demonstrated that the surface and interfacial structures of Cu catalysts, and the solid-gas-liquid interfaces on gas-diffusion electrode (GDE) in CO2 reduction flow cells can be modulated to allow efficient CO2 RR to C2+ products. This approach uses the in situ electrochemical reduction of a CuO nanosheet/graphene oxide dots (CuOC(O)) hybrid. Owing to abundant CuOC interfaces in the CuOC(O) hybrid, the CuO nanosheets are topologically and selectively transformed into metallic Cu nanosheets exposing Cu(100) facets, Cu(110) facets, Cu[n(100) × (110)] step sites, and Cu+ /Cu0 interfaces during the electroreduction step, the faradaic efficiencie (FE) to C2+ hydrocarbons was reached as high as 77.4% (FEethylene ≈ 60%) at 500 mA cm-2 . In situ infrared spectroscopy and DFT simulations demonstrate that abundant Cu+ species and Cu0 /Cu+ interfaces in the reduced CuOC(O) catalyst improve the adsorption and surface coverage of *CO on the Cu catalyst, thus facilitating CC coupling reactions.
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BACKGROUND: Hemodynamic monitoring is imperative for patients with cardiogenic shock undergoing Intra-aortic Balloon Pump (IABP) therapy. Blood pressure monitoring encompasses non-invasive, invasive peripheral arterial pressure (IPAP), and invasive central aortic pressure (ICAP) methods. However, marked disparities exist between IPAP and ICAP. This study examined the discrepancies between IPAP and ICAP and their clinical significance. METHODS: A retrospective analysis was conducted on cardiogenic shock patients who underwent IABP therapy and were admitted to the Coronary Care Unit (CCU) of a tertiary hospital in China from March 2017 to November 2022. The Bland-Altman plot illustrated the discrepancy between IPAP and ICAP. A clinically significant difference between ICAP and IPAP measurements was defined as ≥ 10 mmHg, which could necessitate alterations in blood pressure management according to current guidelines that recommend maintaining a mean arterial pressure (MAP) ≥ 70 mmHg. RESULTS: In total, 162 patients were included in the final analysis. In patients without vasopressors, the difference between ICAP and IPAP was 5.73 mmHg (95% limits of agreement [LOA], -16.98 to 28.44), whereas, in patients with vasopressors, it was 4.36 mmHg (95% LOA, -17.31 to 26.03). ICAP measurements exceeded IPAP in patients undergoing IABP therapy. However, the difference was not statistically significant between the two groups. Multivariate logistic regression revealed that higher serum lactate levels (Odds ratio [OR], 1.14; 95% confidence interval [CI], 1.03-1.27; p = 0.013) and age ≥ 60 years (OR, 13.20; 95% CI, 1.50-115.51; p = 0.020) were associated with an increased likelihood of a clinically significant MAP discrepancy. Conversely, a history of coronary heart disease was associated with a decreased likelihood (OR, 0.34; 95% CI, 0.13-0.90; p = 0.031). CONCLUSIONS: Notable discrepancies between ICAP and IPAP measurements exist in cardiogenic shock patients undergoing IABP therapy. ICAP exceeds IPAP, and factors such as age ≥ 60 years, elevated lactic acid levels, and absence of coronary heart disease contribute to this discrepancy. Enhanced vigilance is warranted for these patients, and the consideration of peripheral invasive monitoring in conjunction with IABP therapy is advised.
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Pressão Arterial , Choque Cardiogênico , Humanos , Pessoa de Meia-Idade , Pressão Sanguínea , Estudos Retrospectivos , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/terapia , Determinação da Pressão ArterialRESUMO
Many G-protein-coupled receptor (GPCR) agonists have been studied for transactivating epidermal growth factor receptor (EGFR) signaling through extracellular or intracellular pathways. Accumulated evidence has confirmed that GPCR transactivation participates in various diseases. However, the clinical application of GPCR transactivation has not been explored, and more translational studies are needed to develop therapies to target GPCR-mediated EGFR transactivation. In cancer patients treated with EGFR inhibitors (EGFRi), especially afatinib, a unique acneiform rash is frequently developed. In this study, we first established the connection between GPCR transactivation and EGFRi-induced skin disease. We examined the ability of three different GPCR agonists to reverse signaling inhibition and ameliorate rash induced by EGFRi. The activation of different agonists follows unique time and kinase patterns. Rats treated with EGFRi show a similar skin phenotype, with rash occurring in the clinic; correspondingly, treatment with GPCR agonists reduced keratinocyte apoptosis, growth retardation and infiltration of inflammatory cytokines by transactivation. This phenomenon demonstrates that EGFR inhibition in keratinocytes regulates key factors associated with rash. Our findings indicate that maintaining EGFR signaling by GPCR agonists might provide a possible therapy for EGFR inhibitor-induced skin toxicities. Our study provides the first example of the translational application of GPCR transactivation in treating diseases.
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Exantema , Dermatopatias , Afatinib , Animais , Receptores ErbB , Humanos , Inibidores de Proteínas Quinases , Ratos , Receptores Acoplados a Proteínas G/metabolismo , Ativação TranscricionalRESUMO
Cancer patients suffer from the toxicity of chemotherapy. Antidote, given as a remedy limiting poison, is an effective way to counteract toxicity. However, few antidotes abrogate chemotoxicity without compromising the therapeutic efficacy. Herein, a rationally designed nanoantidote can neutralize chemo-agents in normal cells but not enter tumors and thus would not interfere with the efficacy of tumor treatment. The nanoantidote, consisting of a dendrimer core wrapped by reductive cysteine, captures Temozolomide (TMZ, the glioblastoma standard chemotherapy). Meanwhile, thanks to the blood-brain barrier (BBB) and the size of the nanoantidote, the nanoantidote cannot enter glioblastoma. In murine models, the nanoantidote distributes in normal tissues without crossing the BBB, so it markedly reduces the chemotoxicity of TMZ and retains the original TMZ therapeutic efficacy. With most nanotechnologies focusing on antitumor treatment, this detoxicating strategy demonstrates a nanoplatform to reduce chemotoxicity using physiology barriers and introduces a new approach to nanomedicine for cancer chemotherapy.
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Neoplasias Encefálicas , Glioblastoma , Animais , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Barreira Hematoencefálica , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Humanos , Camundongos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Plant pathogens are one of the main factors hindering the breeding of cash crops. Pathogens, including oomycetes, fungus, and bacteria, secrete effectors as invasion weapons to successfully invade and propagate in host plants. Here, we review recent advances made in the field of plant-pathogen interaction models and the action mechanisms of phytopathogenic effectors. The review illustrates how effectors from different species use similar and distinct strategies to infect host plants. We classify the main action mechanisms of effectors in plant-pathogen interactions according to the infestation process: targeting physical barriers for disruption, creating conditions conducive to infestation, protecting or masking themselves, interfering with host cell physiological activity, and manipulating plant downstream immune responses. The investigation of the functioning of plant pathogen effectors contributes to improved understanding of the molecular mechanisms of plant-pathogen interactions. This understanding has important theoretical value and is of practical significance in plant pathology and disease resistance genetics and breeding.
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Oomicetos , Doenças das Plantas , Produtos Agrícolas , Interações Hospedeiro-Patógeno , Oomicetos/fisiologia , Melhoramento Vegetal , Doenças das Plantas/microbiologia , Imunidade VegetalRESUMO
Although graphene fiber-based supercapacitors are promising for wearable electronic devices, the low energy density of electrodes and poor cold resistance of aqueous electrolytes limit their wide application in cold environments. Herein, porous nitrogen/sulfur dual-doped graphene fibers (NS-GFs) are synthesized by hydrothermal self-assembly followed by thermal annealing, exhibiting an excellent capacitive performance of 401â F cm-3 at 400â mA cm-3 because of the synergistic effect of heteroatom dual-doping. The assembled symmetric all-solid-state supercapacitor with polyvinyl alcohol/H2 SO4 /graphene oxide gel electrolyte exhibits a high capacitance of 221â F cm-3 and a high energy density of 7.7â mWh cm-3 at 80â mA cm-3 . Interestingly, solar-thermal energy conversion of the electrolyte with 0.1â wt % graphene oxide extends the operating temperature range of the supercapacitor to 0 °C. Furthermore, the photocatalysis effect of the dual-doped heteroatoms increases the capacitance of NS-GFs. At an ambient temperature of 0 °C, the capacitance increases from 0 to 182â F cm-3 under 1â sun irradiation because of the excellent solar light absorption and efficient solar-thermal energy conversion of graphene oxide, preventing the aqueous electrolyte from freezing. The flexible supercapacitor exhibits a long cycle life, good bending resistance, reliable scalability, and ability to power visual electronics, showing great potential for outdoor electronics in cold environments.
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Global fishery resources have been declining for decades, leading some fisheries to collapse. Although the decline is partly due to man-made chemical contamination, causal chemicals have been identified in only a few cases. We conducted consecutive 3-year investigations of embryonic mortality in Taihu Lake, China, including heavily contaminated northern areas, including Zhushan (ZS), Meiliang (ML), and Gonghu (GH), and the less polluted southeastern Suzhou (SZ). In 2016, 65.8% of crucian carp (Carassius carassius) embryos collected from ZS died before hatching, a substantially higher mortality rate than those observed in ML (21.7%), GH (15.2%), and SZ (2.2%). In 2017, the embryonic mortality rates were 38.8% in ZS, 1.3% in ML, 6.9% in GH, and 3.5% in SZ, and these rates strongly correlated with the concentrations of tris(1,3-dichloro-2-propyl)phosphate (TDCIPP): 104.2, 1.8, 4.6, and 4.1 ng/g lipid weight (lw) in embryos from ZS, ML, GH, and SZ, respectively. In 2018, embryonic mortality decreased to 4.0% in ZS and 1.2% in GH, consistent with decreases in embryonic TDCIPP concentrations to 17.1 and 1.5 ng/g lw, respectively. Moreover, the TDCIPP concentrations in dead embryos (70.5-216.8 ng/g lw) were much higher than those in live embryos (1.2-10.5 ng/g lw). Embryonic mortality was also observed in well-controlled laboratory experiments in which wild crucian carp were exposed to TDCIPP at concentrations similar to those measured in embryos collected from Taihu Lake, thus confirming TDCIPP as a causal factor in mass crucian carp embryo mortality in Taihu Lake. TDCIPP thus poses a threat to the sustainability of fisheries worldwide, given the high worldwide production volume of this chemical and its embryonic lethal toxicity.
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Carpas , Poluentes Químicos da Água , Animais , Humanos , Lagos , Compostos Organofosforados , Fosfatos , Poluentes Químicos da Água/toxicidadeRESUMO
Uterine arteriovenous fistula is a rare but life-threatening gynecologic entity. Meanwhile, long-term radiation exposure will do serious harm to doctors' health. So we improve the operation method to reduce the radiation exposure time. The patient, a 24-years-old woman with a history of dilation and curettage, had long-term menorrhagia and anemia. Uterine arteriovenous fistula was confirmed by ultrasonography and computed tomography angiograph. Percutaneous anhydrous ethanol sclerotherapy was performed under the guidance of the X-ray imaging. The patient was followed up for 2 years without recurrence and had normal menstruation. Recently, she is successfully pregnant again. Percutaneous anhydrous ethanol sclerotherapy is a new option treating uterine arteriovenous fistula, which can greatly shorten the irradiation time and reduce the recurrence rate and has no obvious adverse effect on fertility.
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Fístula Arteriovenosa , Escleroterapia , Adulto , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Etanol , Feminino , Humanos , Gravidez , Ultrassonografia , Útero , Adulto JovemRESUMO
AIMS AND OBJECTIVES: This study aimed to implement cluster analysis of self-concept and job satisfaction to identify subgroups in nurses with master's degree and explore the associations of turnover intention with characteristics among these clusters. DESIGN: A cross-sectional study adhering to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). METHODS: A convenience sample of 408 nurses with master's degree in China filled out the survey from 19 November 2019 to 30 December 2019. A sociodemographic questionnaire, the Nurses' Self-Concept Questionnaire (NSCQ), Job Satisfaction Scale (JSS) and Turnover Intention Questionnaire (TIQ) were adopted to collect the data. K-means cluster analysis was implemented on the R software, and data were analysed using SPSS 24.0. RESULTS: Three subgroups were identified based on cluster analysis of NSCQ and JSS subscales in 405 nurses (99.3%) available for statistical analysis, among whom 30.9%, 17% and 48.1% were allocated to these clusters respectively. Turnover intention significantly differed among the three clusters, with cluster 2 having the highest turnover intention and cluster 1 having the lowest turnover intention. Working department, position, professional title, clinical nurse specialist and annual income were factors differentiating TIQ scores in each cluster. CONCLUSIONS: This study identified three clusters of nurses with master's degree and showed that each cluster was associated with the level of turnover intention. The unique characteristics of the three clusters may be also helpful in identifying and providing specific managerial or social support to reduce turnover rates in nurses with master's degree. RELEVANCE TO CLINICAL PRACTICE: Cluster analysis is s an unsupervised machine learning method to identify meaningful subgroups within heterogeneous population based on variables distributions and patterns underlying in the data set. Through clustering, nurses with multi-dimensional characteristics could be allocated into subgroups associated with turnover intention. As a result, nursing managers could provide approaches for each subgroup to reduce turnover intention.
Assuntos
Enfermeiros Clínicos , Recursos Humanos de Enfermagem Hospitalar , China , Análise por Conglomerados , Estudos Transversais , Humanos , Intenção , Satisfação no Emprego , Reorganização de Recursos Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Efficient utilization of dietary fibers (DFs) is important for optimizing feed resource utilization and animal health. The aim of the current study was to assess the effects of DFs with varying physicochemical properties (bulky, viscous, and fermentable) on fermentation kinetics and microbial composition during in vitro fermentation by fecal inoculum from lactating sow. According to the physicochemical properties, three different DFs, lignocellulose (LC), modified cassava starch (MCS) and konjac flour (KF) were selected as bulky fiber, fermentable fiber and viscous fiber respectively. Gas production, short-chain fatty acids (SCFAs) profiles and microbial composition were monitored during the fermentation. RESULTS: Results showed that the gas production in 72 h (GP72h ) ranked as: KF > MCS > LC (P < 0.05). The halftime of asymptotic gas production ranked as: KF < MCS = LC (P < 0.001). At 36 h of fermentation, MCS group showed higher concentrations of formic acid and lactate than LC and KF groups, whereas KF group showed higher concentrations of propionate and butyrate than LC and MCS groups (P < 0.05). At 72 h of fermentation, KF group showed higher concentrations of formic acid, lactate and propionate than LC and MCS groups, whereas MCS group showed higher concentrations of acetate and butyrate than LC and KF groups (P < 0.05). At 36 h of fermentation, Anaerovibrio and Erysipelatoclostridium abundances were higher in KF group, whereas Proteiniclasticum abundance was higher in MCS group. At 72 h of fermentation, the abundance of Fibrobacter in LC group was higher than that in MCS and KF groups. In addition, we also observed that the abundances of certain specific bacteria (Anaerovibrio and Erysipelatoclostridium) were closely related to the SCFAs production (propionate and butyrate) at different fermentation times. CONCLUSION: Collectively, the present study revealed that KF is a fast fermentation fiber which could produce propionate and butyrate rapidly, whereas LC is difficult to be fermented by bacteria. In addition, the fermentation of DFs with different physicochemical properties had divergent impacts on microbial composition and SCFA production. These findings deepen our understanding of the mechanisms of interaction between DFs and intestinal microbiota, and provide new ideas for the rational use of fiber resources in lactating sows. © 2020 Society of Chemical Industry.
Assuntos
Bactérias/metabolismo , Fibras na Dieta/metabolismo , Fezes/microbiologia , Microbioma Gastrointestinal , Suínos/metabolismo , Amorphophallus/química , Amorphophallus/metabolismo , Ração Animal/análise , Animais , Bactérias/classificação , Bactérias/genética , Dieta/veterinária , Fibras na Dieta/análise , Digestão , Ácidos Graxos Voláteis/química , Ácidos Graxos Voláteis/metabolismo , Fermentação , Cinética , Lignina/química , Lignina/metabolismo , Manihot/química , Manihot/metabolismo , Amido/química , Amido/metabolismo , Suínos/microbiologiaRESUMO
BACKGROUND: The efficient utilization of fiber-rich co-products is important for optimizing feed resource utilization and animal health. This study was conducted to evaluate the fermentation characteristics of fiber-rich co-products, which had equal quantities of total dietary fiber (TDF), at different time points using batch in vitro methods. It considered their gas production, short-chain fatty acid (SCFA) production, and microbial composition. RESULTS: The fermentation of wheat bran (WB) and oat bran (OB) showed higher and faster (P < 0.05) gas and SCFA production than corn bran (CB), sugar beet pulp (SBP), and soybean hulls (SH). The α-diversity was higher in the CB, SBP, and SH groups than in the WB and OB groups (P < 0.05). At the phylum level, OB and WB fermentation showed lower (P < 0.05) relative abundance of Actinobacteria than the CB, SBP, and SH groups. At the genus level, OB and WB fermentation increased the Enterococcus population in comparison with the CB, SBP, and SH groups, whereas CB and SBP fermentation improved the relative abundance of the Christensenellaceae R-7 group more than the WB, OB, and SH groups (P < 0.05). CONCLUSION: Overall, WB and OB were rapidly fermented by fecal microbiota, in contrast with SBP, SH, and CB. Fermentation of different fiber-rich co-products with an equal TDF content gives different responses in terms of microbial composition and SCFA production due to variations in their physicochemical properties and molecular structure. © 2020 Society of Chemical Industry.