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1.
EMBO J ; 42(15): e112900, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37350545

RESUMO

The scaffolding protein angiomotin (AMOT) is indispensable for vertebrate embryonic angiogenesis. Here, we report that AMOT undergoes cleavage in the presence of lysophosphatidic acid (LPA), a lipid growth factor also involved in angiogenesis. AMOT cleavage is mediated by aspartic protease DNA damage-inducible 1 homolog 2 (DDI2), and the process is tightly regulated by a signaling axis including neurofibromin 2 (NF2), tankyrase 1/2 (TNKS1/2), and RING finger protein 146 (RNF146), which induce AMOT membrane localization, poly ADP ribosylation, and ubiquitination, respectively. In both zebrafish and mice, the genetic inactivation of AMOT cleavage regulators leads to defective angiogenesis, and the phenotype is rescued by the overexpression of AMOT-CT, a C-terminal AMOT cleavage product. In either physiological or pathological angiogenesis, AMOT-CT is required for vascular expansion, whereas uncleavable AMOT represses this process. Thus, our work uncovers a signaling pathway that regulates angiogenesis by modulating a cleavage-dependent activation of AMOT.


Assuntos
Angiomotinas , Peixe-Zebra , Animais , Camundongos , Peixe-Zebra/metabolismo , Proteínas dos Microfilamentos/metabolismo , Peptídeo Hidrolases , Peptídeos e Proteínas de Sinalização Intercelular/genética
2.
Proc Natl Acad Sci U S A ; 121(25): e2400546121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38857407

RESUMO

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

3.
Proc Natl Acad Sci U S A ; 120(51): e2312876120, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38085783

RESUMO

Electrochemical synthesis of valuable chemicals and feedstocks through carbon dioxide (CO2) reduction in acidic electrolytes can surmount the considerable CO2 loss in alkaline and neutral conditions. However, achieving high productivity, while operating steadily in acidic electrolytes, remains a big challenge owing to the severe competing hydrogen evolution reaction. Here, we show that vertically grown bismuth nanosheets on a gas-diffusion layer can create numerous cavities as electrolyte reservoirs, which confine in situ-generated hydroxide and potassium ions and limit inward proton diffusion, producing locally alkaline environments. Based on this design, we achieve formic acid Faradaic efficiency of 96.3% and partial current density of 471 mA cm-2 at pH 2. When operated in a slim continuous-flow electrolyzer, the system exhibits a full-cell formic acid energy efficiency of 40% and a single pass carbon efficiency of 79% and performs steadily over 50 h. We further demonstrate the production of pure formic acid aqueous solution with a concentration of 4.2 weight %.

4.
Blood ; 142(10): 903-917, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37319434

RESUMO

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.


Assuntos
Proteína 7 Semelhante a Angiopoietina , Proteína 1 Inibidora de Diferenciação , Leucemia Mieloide Aguda , Animais , Camundongos , Proteína 7 Semelhante a Angiopoietina/genética , Proteína 7 Semelhante a Angiopoietina/metabolismo , Medula Óssea/metabolismo , Modelos Animais de Doenças , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Microambiente Tumoral , Humanos , Proteína 1 Inibidora de Diferenciação/metabolismo
5.
J Am Chem Soc ; 146(5): 2928-2932, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38289153

RESUMO

The asymmetric total synthesis of pedrolide (>200 mg) with an unprecedented [5-5-5-6-6-3] hexacyclic core (pedrolane) was achieved. Its unique bicyclo[2.2.1]heptane ring system was efficiently constructed via an enantioselective ene reaction of cyclopentadiene followed by a Wittig reaction, isomerization, and a diastereoselective intramolecular Diels-Alder reaction cascade. The highly oxygenated carane [6-3] ring system was synthesized via a ring-closing metathesis reaction followed by an unusual free carbene cyclopropanation. Furthermore, the 12 contiguous stereocenters of pedrolide were installed diastereoselectively.

6.
J Am Chem Soc ; 146(18): 12681-12690, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38652868

RESUMO

Lithium (Li) metal solid-state batteries feature high energy density and improved safety and thus are recognized as promising alternatives to traditional Li-ion batteries. In practice, using Li metal anodes remains challenging because of the lack of a superionic solid electrolyte that has good stability against reduction decomposition at the anode side. Here, we propose a new electrolyte design with an antistructure (compared to conventional inorganic structures) to achieve intrinsic thermodynamic stability with a Li metal anode. Li-rich antifluorite solid electrolytes are designed and synthesized, which give a high ionic conductivity of 2.1 × 10-4 S cm-1 at room temperature with three-dimensional fast Li-ion transport pathways and demonstrate high stability in Li-Li symmetric batteries. Reversible full cells with a Li metal anode and LiCoO2 cathode are also presented, showing the potential of Li-rich antifluorites as Li metal-compatible solid electrolytes for high-energy-density solid-state batteries.

7.
Small ; 20(16): e2306914, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38041488

RESUMO

Electrocatalysts with high activity and durability for acidic oxygen evolution reaction (OER) play a crucial role in achieving cost-effective hydrogen production via proton exchange membrane water electrolysis. A novel electrocatalyst, Te-doped RuO2 (Te-RuO2) nanotubes, synthesized using a template-directed process, which significantly enhances the OER performance in acidic media is reported. The Te-RuO2 nanotubes exhibit remarkable OER activity in acidic media, requiring an overpotential of only 171 mV to achieve an anodic current density of 10 mA cm-2. Furthermore, they maintain stable chronopotentiometric performance under 10 mA cm-2 in acidic media for up to 50 h. Based on the experimental results and density functional calculations, this significant improvement in OER performance to the synergistic effect of large specific surface area and modulated electronic structure resulting from the doping of Te cations is attributed.

8.
World J Surg Oncol ; 22(1): 21, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243254

RESUMO

BACKGROUND: After radical surgery, early detection of recurrence and metastasis is a crucial factor in enhancing the prognosis and survival of patients with gastric cancer (GC). Therefore, assessing the risk of recurrence in gastric cancer patients and determining the timing for postoperative recurrence is crucial. METHODS: The clinicopathological data of 521 patients with recurrent gastric cancer, who underwent radical gastrectomy at Zhejiang Cancer Hospital between January 2010 and January 2017, were retrospectively analyzed. These patients were randomly divided into two groups: a training group (n = 365) and a validation group (n = 156). In the training set, patients were further categorized into early recurrence (n = 263) and late recurrence (n = 102) groups based on a 2-year boundary. Comparative analyses of clinicopathological features and prognoses were conducted between these two groups. Subsequently, a nomogram for predicting early recurrence was developed and validated. RESULTS: In this study, the developed nomogram incorporated age, serous infiltration, lymph node metastasis, recurrence mode, and the tumour marker CA19-9. In the training cohort, the area under the curve (AUC value) was 0.739 (95% CI, 0.682-0.798), with a corresponding C-index of 0.739. This nomogram was subsequently validated in an independent validation cohort, yielding an AUC of 0.743 (95% CI, 0.652-0.833) and a C-index of 0.743. Furthermore, independent risk factors for prognosis were identified, including age, absence of postoperative chemotherapy, early recurrence, lymph node metastasis, abdominal metastasis, and vascular cancer embolus. CONCLUSION: Independent risk factors for gastric cancer recurrence following radical surgery were utilized to construct a nomogram for predicting early relapse. This nomogram effectively assesses the risk of recurrence, aids in treatment decision-making and follow-up planning in clinical settings, and demonstrated strong performance in the validation cohort.


Assuntos
Nomogramas , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia , Metástase Linfática , Gastrectomia/efeitos adversos
9.
Int J Mol Sci ; 25(12)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38928316

RESUMO

Skin is the largest organ in the human body and requires proper dressing to facilitate healing after an injury. Wounds on movable parts, such as the elbow, knee, wrist, and neck, usually undergo delayed and inefficient healing due to frequent movements. To better accommodate movable wounds, a variety of functional hydrogels have been successfully developed and used as flexible wound dressings. On the one hand, the mechanical properties, such as adhesion, stretchability, and self-healing, make these hydrogels suitable for mobile wounds and promote the healing process; on the other hand, the bioactivities, such as antibacterial and antioxidant performance, could further accelerate the wound healing process. In this review, we focus on the recent advances in hydrogel-based movable wound dressings and propose the challenges and perspectives of such dressings.


Assuntos
Bandagens , Hidrogéis , Cicatrização , Humanos , Hidrogéis/química , Animais , Antibacterianos/uso terapêutico , Pele/lesões
10.
J Am Chem Soc ; 145(31): 17485-17494, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37526148

RESUMO

Converting hydrogen chemical energy into electrical energy by fuel cells offers high efficiencies and environmental advantages, but ultrapure hydrogen (over 99.97%) is required; otherwise, the electrode catalysts, typically platinum on carbon (Pt/C), will be poisoned by impurity gases such as ammonia (NH3). Here we demonstrate remarkable NH3 resistivity over a nickel-molybdenum alloy (MoNi4) modulated by chromium (Cr) dopants. The resultant Cr-MoNi4 exhibits high activity toward alkaline hydrogen oxidation and can undergo 10,000 cycles without apparent activity decay in the presence of 2 ppm of NH3. Furthermore, a fuel cell assembled with this catalyst retains 95% of the initial peak power density even when NH3 (10 ppm)/H2 was fed, whereas the power output reduces to 61% of the initial value for the Pt/C catalyst. Experimental and theoretical studies reveal that the Cr modifier not only creates electron-rich states that restrain lone-pair electron donation but also downshifts the d-band center to suppress d-electron back-donation, synergistically weakening NH3 adsorption.

11.
Microb Pathog ; 185: 106425, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37923181

RESUMO

Rabies, caused by the rabies virus (RABV), is the most fatal zoonotic disease. It is a neglected tropical disease which remains a major public health problem, causing approximately 59,000 deaths worldwide annually. Despite the existence of effective vaccines, the high incidence of human rabies is mainly linked to tedious vaccine immunisation procedures and the overall high cost of post-exposure prophylaxis. Therefore, it is necessary to develop an effective vaccine that has a simple procedure and is affordable to prevent rabies infection in humans. RABV belongs to the genus Lyssavirus and family Rhabdoviridae. Previous phylogenetic analyses have identified seven major clades of RABV in China (China I-VII), confirmed by analysing nucleotide sequences from both the G and N proteins. This study evaluated the immunogenicity and protective capacity of SYS6008, an mRNA rabies vaccine expressing rabies virus glycoprotein, in mice and cynomolgus macaques. We demonstrated that SYS6008 induced sufficient levels of rabies neutralising antibody (RVNA) in mice. In addition, SYS6008 elicited strong and durable RVNA responses in vaccinated cynomolgus macaques. In the pre-exposure prophylaxis murine model, one or two injections of SYS6008 at 1/10 or 1/30 of dosage provided protection against a challenge with a 30-fold LD50 of rabies virus (China I and II clades). We also demonstrated that in the post-exposure prophylaxis murine model, which was exposed to lethal rabies virus (China I-VII clades) before vaccination, one or two injections of SYS6008 at both 1/10 and 1/30 dosages provided better protection against rabies virus challenge than the immunization by five injections of commercial vaccines at the same dosage. In addition, we proved that SYS6008-induced RVNAs could neutralise RABV from the China I-VII clades. Finally, 1/10 of the dosage of SYS6008 was able to stimulate significant RABV-G specificity in the T cell response. Furthermore, we found that SYS6008 induced high cellular immunity, including RABV-G-specific T cell responses and memory B cells. Our results imply that the SYS6008 rabies vaccine, with a much simpler vaccination procedure, better immunogenicity, and enhanced protective capacity, could be a candidate vaccine for post-exposure prophylaxis of rabies infections.


Assuntos
Vacina Antirrábica , Vírus da Raiva , Raiva , Humanos , Animais , Camundongos , Raiva/prevenção & controle , Vacina Antirrábica/genética , Vírus da Raiva/genética , Profilaxia Pós-Exposição/métodos , Modelos Animais de Doenças , Filogenia , Anticorpos Antivirais , Macaca
12.
BMC Cancer ; 23(1): 5, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597055

RESUMO

BACKGROUND: It has been reported that inflammatory and nutritional markers are related to prognosis in numerous malignancies. The present study analyzed the significance of these markers' alterations during neoadjuvant chemotherapy in the long-term outcomes in patients with advanced gastric cancer. METHODS: A retrospective review was performed of 437 advanced gastric cancer patients who underwent a neoadjuvant chemotherapy (NACT) regimen followed by surgical treatment. Inflammatory and nutritional markers measured from the blood samples collected from the patients before the first neoadjuvant chemotherapy and after the last neoadjuvant chemotherapy were used for analysis. Statistical analysis, including Mann-Whitney U or chi-square tests, the Kaplan-Meier method and Cox multivariate analysis, were performed to analyze the predictive value of these markers for overall survival outcomes (OS). RESULTS: Most biomarkers, including lymphocyte, leucocyte, neutrophil, monocyte, platelet, LMR, PLR, SII, CRP, CAR, hemoglobulin and albumin levels, changed during NACT (P <  0.05). After separately grouping the patients based on the normal range of hematologic indexes and the change rate (α) of systemic inflammatory and nutritional markers by the cutoff value derived from X-tile (P <  0.05), we found that differentiation, TRG, pre-NACT BMI, pre-NACT platelet counts, post-NACT lymphocyte counts, the change in lymphocyte counts, change in platelet counts and LMR(α), PLR(α), SII(α), and CAR(α) were associated with OS. Multivariate analysis revealed that PLR (α) > - 19% was correlated with a 3.193-fold (95% CI: 2.194-4.649) higher risk of death (P <  0.001) than others. CONCLUSION: NACT could significantly change several inflammatory and nutritional markers in the perioperative period; the platelet counts before NACT, and the change in lymphocytes during NACT truly correlated with long-term outcomes among patients with advanced gastric cancer. The systemic inflammatory marker PLR may be a reliable marker for the prediction of prognosis.


Assuntos
Neoplasias Gástricas , Humanos , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Linfócitos/patologia , Contagem de Linfócitos , Neutrófilos/patologia , Estudos Retrospectivos , Período Perioperatório
13.
J Oral Pathol Med ; 52(5): 389-401, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36153671

RESUMO

BACKGROUND: Lymph node metastasis can independently predict oral squamous cell carcinoma patients' survival. This study would investigate the genetic and cellular differences between oral squamous cell carcinoma with positive and negative lymph node metastases. METHODS: We gathered single-cell RNA sequencing and bulk gene expression data from the Cancer Genome Atlas and Gene Expression Omnibus databases. Sixty lymph node-metastasis-related genes were discovered with refined single-cell RNA sequencing data analysis, and consensus clustering provided three molecular subtypes of oral squamous cell carcinoma. Least absolute shrinkage and selection operator analyses were then utilized to establish a five-gene risk model. CIBERSORT analysis revealed the immune infiltration profile of different risk subgroups. RESULTS: Oral squamous cell carcinoma patients were classified into three subtypes based on the 60 lymph node-metastasis-related key genes identified by single-cell RNA sequencing data. Patients in Subtype 3 showed a tendency for lymph node metastasis and poorer prognosis. Moreover, five biomarkers were selected from the 60 genes to construct a five-gene risk model evaluating the risk of lymph node metastasis. A lower probability of lymph node metastasis and a better prognosis was observed in the low-risk group. The immune infiltration of three different risk groups was explored with CIBERSORT. Besides, further analysis implied different sensitivities of anticancer drugs, including immunotherapy drugs and targeted compounds, in the three risk groups. CONCLUSION: In view of intratumoral heterogeneity, we found 60 genes associated with lymph node metastasis of oral squamous cell carcinoma. Subsequently, we constructed a five-gene signature that could improve the prediction of lymph node metastasis, clinical outcome, and promote individualized treatment strategies for oral squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Metástase Linfática/genética , Prognóstico , RNA-Seq
14.
BMC Microbiol ; 22(1): 232, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36180838

RESUMO

BACKGROUND: Weedy rice competes for nutrients and living space with cultivated rice, which results in serious reductions in rice production. The rhizosphere bacterial community plays an important role in nutrient competition between species. It is therefore important to clarify the differences in the diversities of the inter rhizosphere bacterial community between cultivated rice and weedy rice. The differences in compositions and co-occurrence networks of the rhizosphere bacterial community of cultivated rice and weedy rice are largely unknown and thus the aim of our study. RESULTS: In our study, the different rhizosphere bacterial community structures in weedy rice (AW), cultivated rice (AY) and cultivated rice surrounded by weedy rice (WY) were determined based on 16S rRNA gene sequencing. The majority of the WY rhizosphere was enriched with unique types of microorganisms belonging to Burkholderia. The rhizosphere bacterial community showed differences in relative abundance among the three groups. Network analysis revealed a more complex co-occurrence network structure in the rhizosphere bacterial community of AW than in those of AY and WY due to a higher degree of Microbacteriaceae and Micrococcaceae in the network. Both network analysis and functional predictions reveal that weedy rice contamination dramatically impacts the iron respiration of the rhizosphere bacterial community of cultivated rice. CONCLUSIONS: Our study shows that there are many differences in the rhizosphere bacterial community of weedy rice and cultivated rice. When cultivated rice was disturbed by weedy rice, the rhizosphere bacterial community and co-occurrence network also changed. The above differences tend to lead to a nutritional competitive advantage for weedy rice in paddy soils.


Assuntos
Burkholderia , Oryza , Burkholderia/genética , Ferro , Oryza/microbiologia , RNA Ribossômico 16S/genética , Rizosfera , Solo/química , Microbiologia do Solo
15.
Blood ; 135(25): 2271-2285, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32202636

RESUMO

SETD2, the histone H3 lysine 36 methyltransferase, previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in myelodysplastic syndromes (MDSs) has been unclear. In this study, low expression of SETD2 correlated with shortened survival in patients with MDS, and the SETD2 levels in CD34+ bone marrow cells of those patients were increased by decitabine. We knocked out Setd2 in NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and found that loss of Setd2 accelerated the transformation of MDS into acute myeloid leukemia (AML). Loss of Setd2 enhanced the ability of NHD13+ hematopoietic stem and progenitor cells (HSPCs) to self-renew, with increased symmetric self-renewal division and decreased differentiation and cell death. The growth of MDS-associated leukemia cells was inhibited though increasing the H3K36me3 level by using epigenetic modifying drugs. Furthermore, Setd2 deficiency upregulated hematopoietic stem cell signaling and downregulated myeloid differentiation pathways in the NHD13+ HSPCs. Our RNA-seq and chromatin immunoprecipitation-seq analysis indicated that S100a9, the S100 calcium-binding protein, is a target gene of Setd2 and that the addition of recombinant S100a9 weakens the effect of Setd2 deficiency in the NHD13+ HSPCs. In contrast, downregulation of S100a9 leads to decreases of its downstream targets, including Ikba and Jnk, which influence the self-renewal and differentiation of HSPCs. Therefore, our results demonstrated that SETD2 deficiency predicts poor prognosis in MDS and promotes the transformation of MDS into AML, which provides a potential therapeutic target for MDS-associated acute leukemia.


Assuntos
Anemia Refratária com Excesso de Blastos/patologia , Calgranulina B/fisiologia , Histona-Lisina N-Metiltransferase/deficiência , Histona-Lisina N-Metiltransferase/fisiologia , Leucemia Mieloide Aguda/etiologia , Anemia Refratária com Excesso de Blastos/genética , Anemia Refratária com Excesso de Blastos/metabolismo , Animais , Calgranulina B/biossíntese , Calgranulina B/genética , Transformação Celular Neoplásica , Células Cultivadas , Decitabina/farmacologia , Regulação para Baixo , Regulação Leucêmica da Expressão Gênica , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/patologia , Código das Histonas/efeitos dos fármacos , Histona-Lisina N-Metiltransferase/biossíntese , Histona-Lisina N-Metiltransferase/genética , Proteínas de Homeodomínio/genética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Síndromes Mielodisplásicas/patologia , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Prognóstico , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Análise Serial de Tecidos , Transcriptoma
16.
Clin Endocrinol (Oxf) ; 96(3): 402-412, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34592016

RESUMO

BACKGROUND: Limited studies have focused on the associated clinicopathologic features and short-term prognostic impacts of metastatic patterns at initial diagnosis in differentiated thyroid cancer (DTC). METHODS: Overall, 530 individuals with distant DTC diagnosed between 2010 and 2014 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Multinomial logistic regression model was used to assess the clinicopathologic factors influencing the pattern of distant metastasis. Kaplan-Meier method and multivariable Cox regression were used to estimate the short-term effects of metastatic patterns on overall (OS) and thyroid cancer-specific survival (TCSS). RESULTS: Fifty, 111, 263, 59 and 47 patients presented with distant lymph node (LN)-only, bone-only, lung-only, bone plus lung, and liver and/or brain metastases (Mets), respectively. Regional lymph node metastasis (LNM) and follicular histotype were the only confirmed risk factors for distant LN-only Mets and bone-only Mets, respectively. Larger tumour size, extrathyroidal extension (ETE) and papillary histotype were associated with lung-only Mets. Synchronous bone and lung Mets were more likely to occur in older patients. In addition, patients with distant LN-only Mets had hardly any negative effect on OS and TCSS, whereas those with synchronous bone and lung or liver/brain Mets predicted unfavourable short-term outcomes, regardless of whether they received total thyroidectomy and radioisotopes. CONCLUSIONS: Different clinicopathologic factors predispose to different patterns of metastases with profound short-term survival differences among DTC patients. Our findings may help to determine effective pretreatment screening for aggressive metastatic patterns at initial diagnosis, and thus to provide additional treatment or access of clinical trials for these patients.


Assuntos
Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Idoso , Humanos , Metástase Linfática , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos
17.
Biomed Chromatogr ; 36(5): e5338, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35028961

RESUMO

Hypertension affects multiple organs in the body during the development of the disease. The antihypertensive effect of acupuncture has been confirmed. How the protective effect of electroacupuncture on the renal cortex of the spontaneously hypertensive rat (SHR) is achieved has not yet been determined. The purpose of this study was to understand the impact of electroacupuncture on the blood pressure of SHRs and the impact on metabolites in the renal cortex, looking for potential differential metabolites and then proceeding to the next step of exploratory research. The experimental animals were divided into four groups: control group, model group, electroacupuncture group and losartan potassium group. Electroacupuncture on bilateral Taichong (LR3) and Zusanli (ST36) lasted for 3 weeks, and the renal cortex was collected for metabonomics research. UHPLC-MS was used to analyze the changes in the metabolic spectrum of renal cortex tissue. The results showed that electroacupuncture can significantly reduce the blood pressure of SHRs. A total of 12 metabolites changed significantly in the comparison between each group and the model group.The possible mechanism is that the primary bile acid biosynthesis, bile secretion, tryptophan metabolism and other metabolic pathways affect the renal cortex.


Assuntos
Eletroacupuntura , Hipertensão , Animais , Pressão Sanguínea , Hipertensão/metabolismo , Hipertensão/terapia , Metabolômica , Ratos , Ratos Endogâmicos SHR
18.
BMC Surg ; 22(1): 401, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36404297

RESUMO

BACKGROUND: Lymph node metastases often occur in advanced gastric cancer, with some patients presenting with metastases in the para-aortic lymph nodes. There are persistent Controversies about the benefit of para-aortic lymph node dissection (PAND). Our purpose is to probe whether PAND following preoperative chemotherapy had any clinical significance in individuals with PALNs in gastric cancer. MATERIAL AND METHODS: To retrospectively analyze the clinical data of 86 gastric cancer patients (40 in the D2 + PAND group and 46 in the D2 group) who attended the abdominal surgery department of Zhejiang Cancer Hospital between September 1, 2008, and July 30, 2018. RESULTS: In the D2 + PAND group (40 cases), the average number of lymph nodes cleared per case was 4.3 in group 16 (16a2, 16b1), and the postoperative pathology confirmed lymph node positivity in 16 cases, with a metastasis rate of 40%. The median overall survival times were 63 and 34 months for the patients in the D2 + PAND group and D2 group, respectively. The 3-year overall survival (OS) compared to the D2 group (D2 + PAND 69.1% vs. D2 50%, P = 0.012) and a statistically significant difference in 3-year disease-free survival (DFS) (D2 + PAND 69.6% vs. D2 38.3%, P = 0.007). Lymph node dissection extent and recurrence of para-aortic lymph nodes were independent prognostic variables for the patients. The recurrence rate was reduced in the D2 + PAND group compared to the D2 group (D2 + PAND 7.5% vs. D2 26.1%, p = 0.023). CONCLUSIONS: For patients with gastric cancer whose imaging suggests metastasis in the para-aortic lymph nodes, preoperative chemotherapy combined with PAND is an effective and safe treatment that may benefit patient survival.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Metástase Linfática , Estudos Retrospectivos , Linfonodos/patologia , Excisão de Linfonodo
19.
Sensors (Basel) ; 22(20)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36298300

RESUMO

SO2F2 and SOF2 are the main components from the decomposition of insulation gas SF6. Photoacoustic spectroscopy (PAS) has been acknowledged as an accurate sensing technique. Polar material adsorption for SO2F2 and SOF2 in the photoacoustic gas cell of PAS may affect detection efficiency. In this paper, the optical gas-cell dynamic adsorptions of four different materials and the detection effects on SO2F2 and SOF2 are theoretically analyzed and experimentally demonstrated. The materials, including grade 304 stainless steel (SUS304), grade 6061 aluminum alloy (Al6061), polyvinylidene difluoride (PVDC), and polytetrafluoroethylene (PTFE), were applied inside the optical gas cell. The results show that, compared with metallic SUS304 and Al6061, plastic PVDC and PTFE would reduce the gas adsorption of SO2F2 and SOF2 by 10 to 20% and shorten the response time during gas exchange. The complete gas defusing period in the experiment was about 30 s. The maximum variations of the 90% rising time between the different adsorption materials were approximately 3 s for SO2F2 and 6 s for SOF2, while the generated photoacoustic magnitudes were identical. This paper explored the material selection for PAS-based gas sensing in practical applications.


Assuntos
Alumínio , Aço Inoxidável , Adsorção , Alumínio/química , Análise Espectral/métodos , Plásticos , Politetrafluoretileno
20.
EMBO Rep ; 20(6)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30979708

RESUMO

Type I interferon (IFN)-induced Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling drives the expression of IFN-stimulated genes (ISGs) to mediate antiviral response. The strength and duration of JAK-STAT signaling are tightly regulated to ensure effective antiviral defense while avoiding pathological inflammation and autoimmunity. Here, we report that cTAZ, an isoform of the Hippo pathway effector TAZ, is transcribed by an alternative promoter. Although majority of C-terminal sequences of TAZ is retained, cTAZ is not regulated by the Hippo signaling and does not mediate its growth-inhibitory functions. Instead, cTAZ negatively regulates JAK-STAT signaling by inhibiting STAT1/2 nuclear localization and ISG expression, and its expression is induced by type I IFN Thus, cTAZ functions as a modulator of JAK-STAT signaling and may play a role in fine-tuning cellular antiviral response.


Assuntos
Janus Quinases/metabolismo , Regiões Promotoras Genéticas , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Transativadores/genética , Transcrição Gênica , Animais , Perfilação da Expressão Gênica , Via de Sinalização Hippo , Humanos , Camundongos , Modelos Biológicos , Fosforilação , Ligação Proteica , Multimerização Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Transporte Proteico , Isoformas de RNA , Fatores de Transcrição STAT/química , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional
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