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1.
J Am Chem Soc ; 146(22): 15446-15452, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38776639

RESUMO

Linker installation is a potent strategy for integrating specific properties and functionalities into metal-organic frameworks (MOFs). This method enhances the structural diversity of frameworks and enables the precise construction of robust structures, complementing the conventional postsynthetic modification approaches, by fully leveraging open metal sites and active organic linkers at targeting locations. Herein, we demonstrated an insertion of a d-camphorate linker into a flexible Zr-based MOF, PCN-700, through linker installation. The resultant homochiral MOF not only exhibits remarkable stability but also functions as a highly efficient luminescent material for enantioselective sensing. Competitive absorption and energy/electron transfer processes contribute to the sensing performance, while the difference in binding affinities dominates the enantioselectivity. This work presents a straightforward route to crafting stable homochiral MOFs for enantioselective sensing.

2.
Phys Rev Lett ; 132(21): 216001, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38856265

RESUMO

We propose a universal spin superconducting diode effect (SDE) induced by spin-orbit coupling (SOC) in systems with spin-triplet correlations, where the critical spin supercurrents in opposite directions are unequal. By analysis from both the Ginzburg-Landau theory and energy band analysis, we show that the spin-↑↑ and spin-↓↓ Cooper pairs possess opposite phase gradients and opposite momenta from the SOC, which leads to the spin SDE. Two superconductors with SOC, a p-wave superconductor as a toy model and a practical superconducting nanowire, are numerically studied and they both exhibit spin SDE. In addition, our theory also provides a unified picture for both spin and charge SDEs.

3.
Microb Cell Fact ; 23(1): 3, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172890

RESUMO

BACKGROUND: Antibiotics biosynthesis is usually regulated by the cluster-situated regulatory gene(s) (CSRG(s)), which directly regulate the genes within the corresponding biosynthetic gene cluster (BGC). Previously, we have demonstrated that LmbU functions as a cluster-situated regulator (CSR) of lincomycin. And it has been found that LmbU regulates twenty non-lmb genes through comparative transcriptomic analysis. However, the regulatory mode of CSRs' targets outside the BGC remains unknown. RESULTS: We screened the targets of LmbU in the whole genome of Streptomyces lincolnensis and found fourteen candidate targets, among which, eight targets can bind to LmbU by electrophoretic mobility shift assays (EMSA). Reporter assays in vivo revealed that LmbU repressed the transcription of SLINC_0469 and SLINC_1037 while activating the transcription of SLINC_8097. In addition, disruptions of SLINC_0469, SLINC_1037, and SLINC_8097 promoted the production of lincomycin, and qRT-PCR showed that SLINC_0469, SLINC_1037, and SLINC_8097 inhibited transcription of the lmb genes, indicating that all the three regulators can negatively regulate lincomycin biosynthesis. CONCLUSIONS: LmbU can directly regulate genes outside the lmb cluster, and these genes can affect both lincomycin biosynthesis and the transcription of lmb genes. Our results first erected the cascade regulatory circuit of LmbU and regulators outside lmb cluster, which provides the theoretical basis for the functional research of LmbU family proteins.


Assuntos
Proteínas de Bactérias , Streptomyces , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Lincomicina , Streptomyces/genética , Streptomyces/metabolismo , Transcriptoma , Regulação Bacteriana da Expressão Gênica , Antibacterianos/farmacologia , Antibacterianos/metabolismo
4.
J Org Chem ; 89(3): 1515-1523, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38253015

RESUMO

Radical cascade cyclization via the cracking of alkenyl C-H has emerged as an attractive and remarkable tool for the rapid construction of ring frameworks with endocyclic double bonds. We developed a cascade reaction of 3-aza-1,5-enynes with sulfur dioxide and cycloketone oxime esters to access cyanoalkylsulfonylated 1,2-dihydropyridines, which can be easily converted to pyridine derivatives. This protocol involves radical addition to the C≡C bond and 6-endo cyclization and features high regioselectivity and a broad substrate scope.

5.
Small ; 19(46): e2303259, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37490527

RESUMO

Sodium-ion batteries (SIBs) are expected to replace partial reliance on lithium-ion batteries (LIBs) in the field of large-scale energy storage as well as low-speed electric vehicles due to the abundance, wide distribution, and easy availability of sodium metal. Unfortunately, a certain amount of sodium ions are irreversibly trapped in the solid electrolyte interface (SEI) layer during the initial charging process, causing the initial capacity loss (ICL) of the SIBs. A separator capacity-compensation strategy is proposed, where the capacity compensator on the separator oxidizes below the high cut-off voltage of the cathode to provide additional sodium ions. This strategy shows attractive advantages, including adaptability to current production processes, no impairment of cell long-cycle life, controlled pre-sodiation degree, and strategy universality. The separator capacity-compensation strategy is applied in the NaNi1/3 Fe1/3 Mn1/3 O2 (NMFO)||HC full cell and achieve a compensated capacity ratio of 18.2%. In the Na3 V2 (PO4 )3 (NVP)||HC full cell, the initial reversible specific capacity is increased from 61.0 mAh g-1 to 83.1 mAh g-1 . The separator capacity-compensation strategy is proven to be universal and provides a new perspective to enhance the energy density of SIBs.

6.
J Basic Microbiol ; 63(2): 190-199, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36453540

RESUMO

Lincomycin produced by Streptomyces lincolnensis is a critical antibacterial antibiotic in the clinical. To further understand the regulatory mechanism of lincomycin biosynthesis, we identified an alternative σ factor, σL sl , in Streptomyces lincolnensis NRRL 2936. Deletion of sigLsl resulted in an increase in cell growth but a decrease in lincomycin production. σL sl boosted lincomycin biosynthesis by directly stimulating the transcription of four genes (lmbD, lmbV, lmrC, and lmbU) within the lincomycin biosynthetic lmb gene cluster. Besides, σL sl participated in lincomycin biosynthesis by directly stimulating the transcription of mshC, a gene responsible for MSH synthesis. In conclusion, our findings demonstrated that σL sl plays a direct regulatory role in lincomycin biosynthesis. This study extends the understanding of molecular mechanisms of lincomycin biosynthetic regulation.


Assuntos
Lincomicina , Fator sigma , Fator sigma/genética , Proteínas de Bactérias/genética , Antibacterianos
7.
World J Microbiol Biotechnol ; 39(12): 332, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37801155

RESUMO

Regulators belonging to the DeoR family are widely distributed among the bacteria. Few studies have reported that DeoR family proteins regulate secondary metabolism of Streptomyces. This study explored the function of DeoR (SLINC_8027) in Streptomyces lincolnensis. Deletion of deoR in NRRL 2936 led to an increase in cell growth. The lincomycin production of the deoR deleted strain ΔdeoR was 3.4-fold higher than that of the wild strain. This trait can be recovered to a certain extent in the deoR complemented strain ΔdeoR::pdeoR. According to qRT-PCR analysis, DeoR inhibited the transcription of all detectable genes in the lincomycin biosynthesis cluster and repressed the expression of glnR, bldD, and SLCG_Lrp, which encode regulators outside the cluster. DeoR also inhibited the transcription of itself, as revealed by the XylE reporter. Furthermore, we demonstrated that DeoR bound directly to the promoter region of deoR, lmbA, lmbC-D, lmbJ-K, lmrA, lmrC, glnR, and SLCG_Lrp, by recognizing the 5'-CGATCR-3' motif. This study found that versatile regulatory factor DeoR negatively regulates lincomycin biosynthesis and cellular growth in S. lincolnensis, which expanded the regulatory network of lincomycin biosynthesis.


Assuntos
Lincomicina , Streptomyces , Lincomicina/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Metabolismo Secundário , Regulação Bacteriana da Expressão Gênica
8.
Ann Hematol ; 101(4): 831-836, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35039900

RESUMO

Idarubicin 12 mg/m2 has been recommended as a standard induction therapy for acute myeloid leukemia (AML). It is unknown whether a higher dose of idarubicin can improve the remission rate. This phase 2 prospective single-arm study enrolled 45 adults with newly diagnosed AML between September 2019 and May 2021 (NCT 04,069,208). Induction therapy included administration of idarubicin 14 mg/m2 for 3 days and cytarabine 100 mg/m2 every 12 h subcutaneously for 7 days. The primary endpoint was the composite complete response rate (complete response (CR) plus complete response with incomplete blood count recovery (CRi)). The median age was 45 years (range 14-60 years). Forty (88.9%) patients had CR or CRi, including 39 patients with CR and 1 patient with CRi after one course of induction therapy. The median times to recovery of absolute neutrophil and platelet counts were 21 days. Only 1 patient died of intracranial hemorrhage during induction therapy. After a median follow-up of 14 months (range 3.5-24 months), the estimated 18-month overall survival and disease-free survival (DFS) were 66.9% and 57.5%, respectively. In conclusion, idarubicin 14 mg/m2 plus cytarabine was a safe and efficient intensive regimen for younger and fit patients with newly diagnosed AML.


Assuntos
Idarubicina , Leucemia Mieloide Aguda , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Adulto Jovem
9.
Biotechnol Bioeng ; 119(12): 3421-3431, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36042572

RESUMO

Nitrilases are promising biocatalysts to produce high-value-added carboxylic acids through hydrolysis of nitriles. However, since the enzymes always show low activity and sometimes with poor reaction specificity toward 2-chloronicotinonitrile (2-CN), very few robust nitrilases have been reported for efficient production of 2-chloronicotinic acid (2-CA) from 2-CN. Herein, a nitrilase from Paraburkholderia graminis (PgNIT) was engineered to improve its catalytic properties. We identified the beneficial residues via computational analysis and constructed the mutant library. The positive mutants were obtained and the activity of the "best" mutant F164G/I130L/N167Y/A55S/Q260C/T133I/R199Q toward 2-CN was increased from 0.14 × 10-3  to 4.22 U/mg. Its reaction specificity was improved with elimination of hydration activity. Molecular docking and molecular dynamics simulation revealed that the conformational flexibility, the nucleophilic attack distance, as well as the interaction forces between the enzyme and substrate were the main reason alternating the catalytic properties of PgNIT. With the best mutant as biocatalyst, 150 g/L 2-CN was completely converted, resulting in 2-CA accumulated to 169.7 g/L. When the substrate concentration was increased to 200 g/L, 203.1 g/L 2-CA was obtained with yield of 85.7%. The results laid the foundation for industrial production of 2-CA with the nitrilase-catalyzed route.


Assuntos
Aminoidrolases , Burkholderiaceae , Ácidos Nicotínicos , Aminoidrolases/química , Aminoidrolases/genética , Aminoidrolases/metabolismo , Burkholderiaceae/genética , Burkholderiaceae/metabolismo , Simulação de Acoplamento Molecular , Especificidade por Substrato , Ácidos Nicotínicos/biossíntese , Ácidos Nicotínicos/metabolismo , Catálise
10.
Inorg Chem ; 61(12): 5017-5024, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35286073

RESUMO

In this study, with the assistance of quaternary ammonium salts we have successfully prepared a new family of salicylate-stabilized heterobimetallic Pb-Ti-oxo clusters, including H(TEA)[Pb2Ti6(µ2-O)2(µ3-O)2(OiPr)4(PA)2(Sal)6(NO3)2] (PTC-321; TEA = tetraethylammonium; HOiPr = isopropanol; H2PA = phenylphosphonic acid; H2Sal = salicylic acid), {PbTi3(µ2-O)(µ3-O)(OiPr)2(PA)(Sal)3(DMF)·CH3CN}n (PTC-322; DMF = dimethylformamide), {PbTi5(µ3-O)6(Sal)3(CH3COO)2(DMF)(OiPr)2}n (PTC-323), [Pb2Ti4(Sal)6(EtO)2(OiPr)6(HOiPr)2]·CH3NH2 (PTC-324; EtOH = CH3CH2OH), H[Pb4Ti9(µ2-O)2(µ3-O)(µ4-O)6(Sal)7(OiPr)13] (PTC-325), and Pb2Ti12(µ2-O)3(µ3-O)3(µ4-O)4(Sal)4(OEt)24 (PTC-326). Single-crystal X-ray diffraction studies demonstrate that the {Ti3Pb(Sal)3} unit acts as the building block to constitute the diverse assembly of PTC-321-PTC-323. Thereinto, the clusters in PTC-322 and PTC-323 are connected into infinite one-dimensional chains. Furthermore, the solvent effects have facilitated the heterobimetallic Pb-Ti-oxo clusters into various configurations in PTC-323-PTC-326. Solid-state ultraviolet-visible spectroscopy analysis indicates that the optical absorption bands of these compounds shift effectively toward the visible-light region, and they were also employed as electrode precursors to investigate their visible-light-driven photocurrent response.

11.
J Gen Intern Med ; 36(10): 3023-3030, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33511569

RESUMO

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) can be treated with intensive therapy, low-intensity therapy, or best supportive care. Medical decision-making might be affected by physicians' occupational and non-occupational factors. OBJECTIVE: To explore the impact of physicians' personalities and behavioral traits on treatment-related decision-making for elderly AML patients. DESIGN: A nationwide cross-sectional survey. PARTICIPANTS: Hematologists in mainland China (N = 529; response rate 64.5%). MAIN MEASURES: The medical decision-making for elderly AML patients was evaluated using 6 clinical vignettes. Hematologists' attitudes toward risk and uncertainty, Big Five personality traits, and decision-making styles were assessed using binary lottery choices and well-recognized self-report inventories. KEY RESULTS: The resulting binary regression model in predicting treatment intensity contained professional title group (OR = 0.012, 95% CI 0.001 to 0.136, P < 0.001), conscientiousness (OR = 0.336, 95% CI 0.121 to 0.932, P = 0.036), extraversion (OR = 0.403, 95% CI 0.166 to 0.974, P = 0.044), conscientiousness by title group (OR = 2.009, 95% CI 1.100 to 3.667, P = 0.023), and extraversion by title group (OR = 1.627, 95% CI 0.965 to 2.743, P = 0.068) as predictors of therapy intensity preference. Junior physicians with a higher level of extraversion (mean difference = 0.27; 95% CI 0.07 to 0.45; P = 0.009) or conscientiousness (mean difference = 0.19; 95% CI 0.01 to 0.36; P = 0.028) tended to prescribe more intensive therapy. Meanwhile, no significant correlation was found between physicians' personalities or behavioral traits and treatment-related decision-making in senior physicians. CONCLUSIONS: Physicians' personalities contribute to treatment-related decision-making for elderly AML patients, depending on the professional titles. More extravert or conscientious attending physicians tended to prescribe more intensive therapy. Meanwhile, the decisions made by chief and associate chief physicians were not impacted by their personal traits. Junior physicians should be aware of such potential influence when making medical decisions.


Assuntos
Leucemia Mieloide Aguda , Médicos , Idoso , Tomada de Decisão Clínica , Estudos Transversais , Tomada de Decisões , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Personalidade
12.
J Sci Food Agric ; 101(11): 4672-4680, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-33491773

RESUMO

BACKGROUND: Purple corn (Zea mays L.) is one of the main economic crops in China and has been used in the treatment of cystitis, urinary infections and obesity. However, purple corncobs, the by-product remaining after processing and having an intense purple-black color, are normally disposed of as waste or used as animal feed. Therefore, to further expand the medicinal value of purple corncob, its content was analyzed and, after purification, the effect and mechanism of purified purple corncob anthocyanins (PPCCA) on CCl4 -induced chronic liver injury in mice were investigated. RESULTS: It was observed that the total anthocyanin content (TAC) from PPCCA (317.51 ± 9.30 mg cyanidin 3-O-glucoside (C-3-G) g-1 dry weight) was significantly higher than that from the purified purple corn seed anthocyanin (266.73 ± 3.67 mg C-3-G g-1 dry weight), of which C-3-G accounted for 90.6% and 90.4% of the TAC, respectively. Furthermore, compared with the CCl4 group, PPCCA treatment significantly reduced liver index, serum total bilirubin, alanine transaminase, aspartate transaminase and liver malondialdehyde levels, but increased liver superoxide dismutase activity. The pathological changes were also improved, such as more regular arrangement of hepatocytes, less swelling, and fewer vacuoles and apoptotic cells. Additionally, mechanistic studies showed that PPCCA downregulated the expression of Caspase-3, Bax and cytochrome P450 2E1 proteins in the liver and upregulated the expression of Bcl-2. CONCLUSION: These results demonstrated that PPCCA could ameliorate CCl4 -induced chronic liver injury by regulating oxidative stress and hepatocyte apoptosis pathways. © 2021 Society of Chemical Industry.


Assuntos
Antocianinas/administração & dosagem , Apoptose/efeitos dos fármacos , Hepatopatias/tratamento farmacológico , Fígado/lesões , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Zea mays/química , Animais , Aspartato Aminotransferases/metabolismo , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias/genética , Hepatopatias/metabolismo , Hepatopatias/fisiopatologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Sementes/química
13.
J Med Virol ; 92(11): 2804-2812, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32542750

RESUMO

A pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. We conducted a retrospective, multicenter study, and followed-up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with real-time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal-viral excretion times among groups with different antiviral regiments were compared with Kaplan-Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Children have lower susceptibility of SARS-CoV-2 infection, longer incubation, and fecal-viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine.


Assuntos
COVID-19/epidemiologia , Fezes/virologia , SARS-CoV-2/fisiologia , Eliminação de Partículas Virais , Adolescente , Antivirais/uso terapêutico , COVID-19/transmissão , Portador Sadio/epidemiologia , Portador Sadio/virologia , Criança , Pré-Escolar , China/epidemiologia , Família , Feminino , Hospitalização , Humanos , Incidência , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/patogenicidade
14.
J Clin Lab Anal ; 34(12): e23521, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32844469

RESUMO

BACKGROUND: Mounting evidence indicates that circular RNAs (circRNAs) could play a pivotal role in cancers. However, due to the lack of sensitive biomarkers, most lung cancer in Xuanwei (LCXW) patients are still diagnosed at an advanced stage accompany with distant metastasis. METHODS: According to the stage of LCXW patients and tissue sources, circRNAs microarray detection was carried out in six groups. Considering fold change, raw intensity, the length of circRNAs, and P-value, we selected eightcircRNAs for further study. A total of 50 paired LCXW tissues were carried out real-time quantitative polymerase chain reaction (RT-qPCR) in order to extended sample size to verify the expression of these circRNAs. RESULTS: We designed 13 617 human circRNA probes for the human circular RNA microarray, detected 10 819 circRNA in six groups of samples; 537 circRNAs were differentially expressed consistently in every stage. Through RT-qPCR, we selected 8 circRNAs, three of which were upregulated (hsa_circ_0005927, hsa_circ_0069397 and hsa_circ_0000937) and five were downregulated (hsa_circ_0001936, hsa_circ_0005255, hsa_circRNA_406010, hsa_circ_0007064, hsa_circ_0000907) in tumor tissues, only hsa_circ_0001936 showed the opposite expression between microarray and RT-qPCR, others were consistent. Additionally, hsa_circ_0005927 and hsa_circ_0001936 were significantly correlated with tumor size, and hsa_circRNA_406010 was related to the prognosis of LCXW patients. CONCLUSION: Together, these results suggest that hsa_circ_0005927, hsa_circ_0001936, and hsa_circRNA_406010 may serve as the novel potential biomarkers for LCXW. Moreover, these results may provide a new insight for the pathogenesis of LCXW.


Assuntos
Neoplasias Pulmonares , RNA Circular , Transcriptoma/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , China , Feminino , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Circular/análise , RNA Circular/genética , RNA Circular/metabolismo
16.
Ann Hematol ; 98(5): 1095-1100, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30511139

RESUMO

Light chain-associated Fanconi syndrome (LCFS) is a disorder of renal proximal tubule due to immunoglobulin light chains. Cases of LCFS are rare and mostly sporadically reported, and treatment of this entity is still controversial. This single-center retrospective study included 22 patients diagnosed with LCFS in Peking Union Medical College Hospital. Monoclonal gammopathy of undetermined significance was diagnosed in 13 patients, and overt multiple myeloma in six patients, with two smoldering myeloma and one Waldenstrom macroglobulinemia. Light chain was mostly kappa type (90.9%). Baseline median estimated glomerular filtration rate was 66 (13-126) ml/min/1.73 m2, with one patient presented as end-stage renal disease. After a median follow-up of 37 months, three patients died. Twelve patients were treated with chemotherapy, including 7 with bortezomib-based regimens. Renal function was significantly improved in the group of patients who received chemotherapy (p = 0.026). Compared with other chemotherapy regimens, patients with bortezomib-based treatment had a better hematological response (p = 0.027) as well as a better proximal tubule outcome (p = 0.015). Chemotherapy likely outweighs supportive treatment in patients with LCFS. Bortezomib-based regimen seems to be a safe first-line therapy for management of those patients.


Assuntos
Bortezomib/administração & dosagem , Síndrome de Fanconi , Taxa de Filtração Glomerular , Túbulos Renais/fisiopatologia , Adulto , Idoso , Bortezomib/efeitos adversos , Síndrome de Fanconi/tratamento farmacológico , Síndrome de Fanconi/fisiopatologia , Feminino , Seguimentos , Humanos , Cadeias Leves de Imunoglobulina , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/fisiopatologia , Estudos Retrospectivos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/fisiopatologia
17.
Cancer Cell Int ; 18: 215, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30598640

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous disease. The survival of older patients is generally poor. In the current study, we sought to investigate the differences in molecular gene mutations between younger and older AML patients, and to identify those newly diagnosed AML patients who are more likely to respond to standard cytarabine and daunorubicin induction chemotherapy. METHODS: We retrospectively evaluated 179 patients who were newly diagnosed with non-M3 AML. A next-generation sequencing assay covering 34 genes was used to investigate recurrently mutated genes. The mutational status of fusion genes was determined by real time PCR. RESULTS: The median age at diagnosis was 53 years (range 18-88 years). Sixty-eight patients were 60 years or older with a median age of 67 years (range 60-88 years). Eighteen patients (10.1%) carried t(8;21)(q22;q22.1) or RUNX1-RUNX1T1 gene fusion, and there was a significantly higher incidence in younger patients (p = 0.019). At least one non-synonymous gene mutation was detected in 159 patients (88.8%). The median number of gene mutations was two (range 0-6). The mean number of molecular gene mutations at diagnosis was higher in older patients than younger patients (2.5 vs 1.83, p = 0.003). Older patients had significantly higher incidences of ASXL1 (22.1% vs 13.5%, p = 0.025) and TP53 mutations (13.2% vs 3.6%, p = 0.034). In total, 78 patients received DA60 (daunorubicin 60 mg/m2 per day on days 1-3 and cytarabine 100 mg/m2 twice per day on days 1-7) as the induction therapy, and information was available on their response to induction treatment. Patients with RUNX1-RUNX1T1 gene fusion were significantly more likely to achieve complete remission (CR) after DA60 induction therapy (p = 0.026), as were patients without the ASXL1 mutation (p = 0.007). CONCLUSION: Older AML patients had a lower incidence of favorable cytogenetics and higher frequencies and burdens of molecular mutations that are associated with poor prognosis compared to younger patients. Patients with RUNX1-RUNX1T1 gene fusion or without the ASXL1 gene mutation had a better chance of achieving CR when treated with cytarabine and daunorubicin induction chemotherapy.

18.
J Cardiovasc Magn Reson ; 20(1): 2, 2018 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-29298704

RESUMO

BACKGROUND: Cardiac impairment is associated with high morbidity and mortality in immunoglobulin light chain (AL) type amyloidosis, for which early identification and risk stratification is vital. For myocardial tissue characterization, late gadolinium enhancement (LGE) is a classic and most commonly performed cardiovascular magnetic resonance (CMR) parameter. T1 mapping with native T1 and extracellular volume (ECV) are recently developed quantitative parameters. We aimed to investigate the prognostic value of native T1, ECV and LGE in patients with AL amyloidosis. METHODS: Eighty-two patients (55.5 ± 8.5 years; 52 M) and 20 healthy subjects (53.2 ± 11.7 years; 10 M) were prospectively recruited. All subjects underwent CMR with LGE imaging and T1 mapping using a Modified Look-Locker Inversion-recovery (MOLLI) sequence on a 3 T scanner. Native T1 and ECV were measured semi-automatically using a dedicated CMR software. The left ventricular (LV) LGE pattern was classified as none, patchy, and global groups. Global LGE was considered when there was diffuse, transmural LGE in more than half of the short axis images. Follow-up was performed for all-cause mortality using Cox proportional hazards regression analysis and Kaplan-Meier survival curves. RESULTS: The patients demonstrated an increase in native T1 (1438 ± 120 ms vs. 1283 ± 46 ms, P = 0.001) and ECV (43.9 ± 10.9% vs. 27.0 ± 1.7%, P = 0.001) compared to healthy controls. Native T1, ECV and LGE showed significant correlation with Mayo Stage, and ECV and LGE showed significant correlation with echocardiographic E/E' and LV ejection fraction. During the follow-up for a median time of 8 months, 21 deaths occurred. ECV ≥ 44.0% (hazard ratio [HR] 7.249, 95% confidence interval (CI) 1.751-13.179, P = 0.002) and global LGE (HR 4.804, 95% CI 1.971-12.926, P = 0.001) were independently prognostic for mortality over other clinical and imaging parameters. In subgroups with the same LGE pattern, ECV ≥ 44.0% remained prognostic (log rank P = 0.029). Median native T1 (1456 ms) was not prognostic for mortality (Tarone-Ware, P = 0.069). CONCLUSIONS: During a short-term follow-up, both ECV and LGE are independently prognostic for mortality in AL amyloidosis. In patients with a similar LGE pattern, ECV remained prognostic. Native T1 was not found to be a prognostic factor.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Volume Sistólico , Função Ventricular Esquerda , Adulto , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Estudos de Casos e Controles , Causas de Morte , China , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo
19.
Pharmazie ; 69(12): 909-16, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25951665

RESUMO

The effect of venlafaxine on the expression of brain-derived neurotrophic factor (BDNF) in rat hippocampal neurons was studied, as well as its inhibitory effect on apoptosis of hippocampal neurons. Differences in behavioral ability between the depression model group and the venlafaxine treatment group were observed in behavioral, sucrose-water and open field tests. The rat hippocampal tissue was sliced, stained and observed for BDNF distribution by immunohistochemistry. Apoptosis of hippocampal neurons was detected by TUNEL. BDNF expression in the hippocampal tissue was detected by Western blot. Injury and apoptosis of the hippocampal tissue were observed by electron microscopy. Behavioral test showed that venlafaxine effectively improved the behavioral abilities of depressed rats. Immunohistochemistry showed that venlafaxine markedly increased BDNF expression in the rat hippocampus. TUNEL showed that venlafaxine markedly inhibited apoptosis of hippocampal neurons, which was also confirmed by electron microscopic observation of the pathologic sections. Venlafaxine improved the expression of BDNF by influencing the PI3k/PKB/eNOS pathway and repressed the apoptosis of hippocampal neurons.


Assuntos
Apoptose/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Cicloexanóis/farmacologia , Depressão/metabolismo , Depressão/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Neurônios/metabolismo , Neurônios/patologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Óxido Nítrico/metabolismo , Células Piramidais/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Cloridrato de Venlafaxina , Aumento de Peso/efeitos dos fármacos
20.
PLoS One ; 19(5): e0304109, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38781194

RESUMO

With the advancement of computer-based testing, log file data has drawn considerable attention from researchers. Although emerging studies have begun to explore log file data, there is a gap in the exploitation of log file data for capturing and understanding participants' cognitive processes. The debate on how to maximize insights from log file data has not yet reached a consensus. Therefore, we present this protocol for a scoping review that aims to characterize the application of log file data in current publications, including the data pre-processing techniques, analytical methodologies, and theoretical frameworks used by researchers. This review will also aim to illuminate how log file data can enhance psychological and educational assessments. Our findings will highlight the opportunities and challenges presented by log file data as an emerging and essential source of evidence for future advancements in psychological and educational assessment.


Assuntos
Avaliação Educacional , Humanos , Avaliação Educacional/métodos , Testes Psicológicos
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