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1.
Fitoterapia ; 153: 104948, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34087409

RESUMO

A norbisabolane and an arabitol benzoate, Talaromarnine A (1), Talaromarnine B (2), together with eight known compounds were obtained from cultures of Talaromyces marneffei, an endophytic fungus of Epilobium angustifolium. Their structures were elucidated by IR, MS, 1D and 2D NMR spectra, and their absolute configuration was determined by single-crystal X-ray diffraction and molecular computation. These compounds were tested for monoamine oxidase, acetylcholinesterase and PI3K inhibitory activity, but no compounds exhibited significant activities.

2.
J Burn Care Res ; 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34089615

RESUMO

Both silicone gel and quercetin are effective in scar treatment but have different action mechanisms. Quercetin is mainly applied in the gel form and can lead to poor adhesion of silicone gel sheet; therefore, they cannot be combined in clinical use. In this study, a silicone gel sheet that releases quercetin in a sustained manner for 48 hours was successfully developed. Four round scars (Ø: 1 cm) were made in the ears of New-Zealand albino rabbits (n=10). After scar healing, the rabbits were divided into four groups: blank control group with no treatment, silicone gel sheet group with dressing change every 2 days, quercetin group with dressing change 3 times daily, and combination treatment group with dressing change every 2 days. Scar assessment was performed 3 months later. Transepidermal water loss showed no difference between the combination treatment group and the silicone gel sheet group, but was lower than that in the quercetin group and the blank control group. Immunohistochemistry of CD 31 and proliferating cell nuclear antigen showed the following results: combination treatment group < silicone gel sheet group = quercetin group < blank control group. Polymerase chain reaction results showed that the expression of type-I and type-III collagen in the combination treatment group and the quercetin group was significantly lower than that in the other two groups. Thus, quercetin-modified silicone gel sheet combines the advantages of the two treatments and is more effective at inhibiting cell proliferation in scar tissue than either of the two treatments alone.

3.
J Tradit Chin Med ; 41(3): 471-478, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34114406

RESUMO

OBJECTIVE: To investigate the efficacy of icariin for healing skull defects in rabbit models. METHODS: Thirty-six 3-month-old female New Zealand white rabbits, weighing 1.8-2.0 kg each, were randomly divided into either the control or experimental group. Skull defect models were constructed in both groups, with the experimental group receiving oral icariin afterwards. At 4, 8 and 12 postoperative weeks, the rabbits were euthanized, and X-rays and samples were taken. Tissue sections were stained using hematoxylin and eosin, followed by additional processing using histological and bone metrological methods for observing the rate and quality of the bone formation. RESULTS: Histologically, additional mature lamellar bone formed in the defect area in the experimental group compared with that of the control group. Bone metrological methods showed that the bone mass, trabecular bone width and number of osteoblasts in the experimental group were significantly higher than those of the control group (P < 0.01). The number of osteoclasts did not significantly differ between the two groups (P > 0.05). CONCLUSION: Icariin increased the bone mass and improved the condition of the defect area in the rabbit skulls.

4.
Hematol Oncol ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061378

RESUMO

Extranodal natural killer (NK)/T-cell lymphoma (NKTL) is a rare non-Hodgkin lymphoma that rarely arise exclusively in or metastasizes to the central nervous system (CNS). Globally, CNS involvement of NKTL heralds a serious prognosis and there is no standard treatment. 19 of 414 patients (4.59%) with ENKL followed were diagnosed with CNS involvement between 2006 and 2020. Two patients had primary CNS (PCNS) NKTL, and 17 patients had secondary CNS (SCNS) invasion. A total of 9 patients survived and 10 patients died. The median overall survival time was 55 months, and the median survival time after CNS invasion was 17 months. The 5-year cumulative survival probability was 45.7%. In conclusion, CNS risk evaluation and prophylaxis treatment can be carried out for patients with NK/T-cell lymphoma prognostic index risk group III/IV. In terms of treatment, systemic therapy based on methotrexate combined with radiotherapy and intrathecal chemotherapy can be selected.

6.
Nat Nanotechnol ; 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972760

RESUMO

Bioorthogonal catalysis mediated by transition metals has inspired a new subfield of artificial chemistry complementary to enzymatic reactions, enabling the selective labelling of biomolecules or in situ synthesis of bioactive agents via non-natural processes. However, the effective deployment of bioorthogonal catalysis in vivo remains challenging, mired by the safety concerns of metal toxicity or complicated procedures to administer catalysts. Here, we describe a bioorthogonal catalytic device comprising a microneedle array patch integrated with Pd nanoparticles deposited on TiO2 nanosheets. This device is robust and removable, and can mediate the local conversion of caged substrates into their active states in high-level living systems. In particular, we show that such a patch can promote the activation of a prodrug at subcutaneous tumour sites, restoring its parent drug's therapeutic anticancer properties. This in situ applied device potentiates local treatment efficacy and eliminates off-target prodrug activation and dose-dependent side effects in healthy organs or distant tissues.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34027654

RESUMO

Microsized SiOx has been vigorously investigated as an advanced anode material for next-generation lithium-ion batteries. However, its practical application is seriously hampered by its huge volume variation during the repeated (de)lithiation process, which destroys the microparticle structure and results in rapid capacity fading. Herein, we propose the usage of trans-difluoroethylene carbonate (DFEC) as an electrolyte additive to maintain the structural integrity of microsized SiOx with a uniform carbon layer (SiOx@C). Compared with ethylene carbonate and fluoroethylene carbonate, DFEC has lower lowest unoccupied molecular orbital energy and higher reduction potential, which is easily reduced and promotes the in situ formation of a more stable LiF-rich solid electrolyte interphase (SEI) on the surface of anode materials. The LiF-rich SEI exhibits enhanced mechanical rigidity and ionic conductivity, thus enabling the microsized SiOx@C anodes' excellent lithium storage stability and high average Coulombic efficiency.

8.
Trends Biochem Sci ; 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34053843

RESUMO

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are among the most ancient small RNAs in all domains of life and are generated by the cleavage of tRNAs. Emerging studies have begun to reveal the versatile roles of tsRNAs in fundamental biological processes, including gene silencing, ribosome biogenesis, retrotransposition, and epigenetic inheritance, which are rooted in tsRNA sequence conservation, RNA modifications, and protein-binding abilities. We summarize the mechanisms of tsRNA biogenesis and the impact of RNA modifications, and propose how thinking of tsRNA functionality from an evolutionary perspective urges the expansion of tsRNA research into a wider spectrum, including cross-tissue/cross-species regulation and harnessing of the 'tsRNA code' for precision medicine.

9.
Plant Dis ; 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34003037

RESUMO

Wheat dwarf virus (WDV, genus Mastrevirus, family Geminiviridae) is an economically important and widespread pathogen of cereal crops. It causes huge yield loss in wheat due to the unavailability of resistant varieties and rapid transmission by the vector leafhopper, Psammotettix alienus (Dahlb). To monitor and forecast this viral disease, an early diagnosis method is required for WDV detection in both infected plants and the virus vectors. In this study, we developed a real-time loop-mediated isothermal amplification (LAMP) assay for WDV detection. The positive sample could be detected within 28-32 min by following a simple and cost-effective procedure. The real-time LAMP assay showed a sensitivity of 2.7×105-6 copies/µL for detection and a high specificity for WDV amplification, with a similar accuracy to qPCR. Furthermore, a tube-closed dye method facilitates the inspection of the LAMP reaction and avoids cross contamination in the detection of the virus. This valuable detection assay could serve as an important tool for diagnosis and forecasting wheat dwarf disease intensity in the field.

10.
Water Res ; 200: 117249, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34051460

RESUMO

At present, a large amount of landfill sludge(LS) has been accumulated all over the world. For environmental and engineering purposes, there is an urgent need for deep dewatering and volume reduction of LS. The deep dewatering of LS mainly uses the method of chemical preconditioning and mechanical dewatering, which is easy to cause environmental pollution and is not conducive to the subsequent resource treatment of LS. To find a more environmentally friendly and efficient method for deep dewatering of LS, an in-situ treatment method combining freeze-thaw and vacuum preloading was proposed. In this paper, based on the existing research, through compression consolidation test and MIP, SEM micro test, the consolidation properties and microstructure of LS after freeze-thaw and chemical preconditioning were studied, and the vacuum consolidation principle of different preconditioning was explored. The results show that: Both FeCl3 and freeze-thaw preconditioning can increase the permeability coefficient and consolidation coefficient by one to two orders of magnitude; After freeze-thaw preconditioning, the void ratio of sludge decreases and the permeability coefficient increases; Under low consolidation pressure, the mechanical properties of the two kinds of pretreated sludge changed significantly; The original sludge is mainly composed of small pores. After FeCl3 conditioning, the large pores and mesopores increased significantly, while the small pores decreased. After freeze-thaw, the large pores and mesopores increase greatly, while the small pores decrease greatly; The original sludge is in the form of a dispersive flocculent structure with many impurities. After freeze-thaw, the intercluster pores increase, showing a honeycomb structure. After FeCl3 conditioning, the sludge structure is more compact and uniform. The change of microstructure and consolidation characteristics of sludge after conditioning reflects the difference of two different preconditioning mechanisms.

11.
Protein Expr Purif ; 186: 105907, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34022391

RESUMO

For recombinant proteins produced in Chinese hamster ovary (CHO) cells, fragmentation is a common phenomenon that results in generation of product-related low-molecular-weight (LMW) species. Recently while purifying a bispecific antibody (bsAb), we observed that the target protein experienced cleavage at a couple of potential sites, leading to truncated products. Further studies suggest that the cleavage can likely be attributed to residual CHO cell protease activity. In order to maximally remove potential protease(s) that contribute fragmentation, we optimized Protein A chromatography by adding sodium caprylate (SC) to the wash buffer. Upon optimization, fragmentation of Protein A eluate happened to a much lesser degree as compared to that of eluate from unoptimized process, and the increased sample stability is in accordance with significantly reduced host cell protein (HCP) level. Taken together, the data suggest that SC wash during Protein A chromatography is an effective means for removing HCPs including endogenous protease(s) that are responsible for target antibody fragmentation.

12.
Reprod Biol ; 21(2): 100505, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33862590

RESUMO

The placenta develops from the outer trophoblastic layer following the differentiation of the fertilized ovum and is therefore more susceptible to epigenetic regulatory changes caused by environmental interventions and influences during assisted reproductive technology. Furthermore, the placenta regulates the development of the fetal heart, brain, kidneys, bones, and other tissues and organs [1]. Placental dysplasia leads to poor perinatal outcomes as well as long-term health risks later in life, including neurodevelopmental disorders, tumors, and adult metabolic syndrome [2,3]. In view of the decisive role of the placenta during intrauterine fetal development, Graham J. Burton, an expert in placentology from the University of Cambridge, formally proposed the theory of "placenta-derived chronic diseases" in 2018 based on embryonic-derived diseases [4]. In this review, we summarized the changes in placental morphology and structure, growth dynamics, imprinted and non-imprinted genes, and other aspects attributable to assisted reproduction technology. Our review provides a theoretical basis for further research on placental changes caused by assisted reproductive technology that are most strongly associated with an increased risk of neonatal long-term diseases.

13.
Mol Med Rep ; 23(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33846791

RESUMO

Propofol­based anesthesia has been reported to reduce the recurrence and metastasis of a number of cancer types following surgical resection. However, the effects of propofol in bladder cancer (BC) are yet to be fully elucidated. The aim of the present study was to investigate the functions of propofol in BC and their underlying mechanisms. In the study, the expression of microRNA (miR)­145­5p in BC tissues and cell lines was evaluated using reverse transcription­quantitative PCR, and the effects of propofol on BC cells were determined using cell viability, wound healing and Transwell cell invasion assays, bioinformatics analysis, western blotting, immunohistochemistry and in vivo tumor xenograft models. It was found that propofol significantly suppressed the proliferation, migration and invasion of BC cells in vitro. In addition, propofol induced miR­145­5p expression in a time­dependent manner, and miR­145­5p knockdown attenuated the inhibitory effects of propofol on the proliferation, migration and invasion of BC cells. Topoisomerase II α (TOP2A) was a direct target of miR­145­5p, and silencing TOP2A reversed the effects of miR­145­5p knockdown in propofol­treated cells. Furthermore, propofol suppressed tumor xenograft growth, which was partially attenuated by miR­145­5p knockdown. The present study provided novel insight into the advantages of surgical intervention with propofol anesthesia in patients with BC.

14.
J Am Chem Soc ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33843219

RESUMO

Li+-conductive ceramic oxide electrolytes, such as garnet-structured Li7La3Zr2O12, have been considered as promising candidates for realizing the next-generation solid-state Li-metal batteries with high energy density. Practically, the ceramic pellets sintered at elevated temperatures are often provided with high stiffness yet low fracture toughness, making them too brittle for the manufacture of thin-film electrolytes and strain-involved operation of solid-state batteries. The ceramic powder, though provided with ductility, does not yield satisfactorily high Li+ conductivity due to poor ion conduction at the boundaries of ceramic particles. Here we show, with solid-state nuclear magnetic resonance, that a uniform conjugated polymer nanocoating formed on the surface of ceramic oxide particles builds pathways for Li+ conduction between adjacent particles in the unsintered ceramics. A tape-casted thin-film electrolyte (thickness: <10 µm), prepared from the polymer-coated ceramic particles, exhibits sufficient ionic conductivity, a high Li+ transference number, and a broad electrochemical window to enable stable cycling of symmetric Li/Li cells and all-solid-state rechargeable Li-metal cells.

15.
Autism ; : 13623613211004054, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845648

RESUMO

LAY ABSTRACT: The Autism Spectrum Rating Scale is a behavioural rating scale completed by parents and teachers that is useful for identifying children with an autism spectrum disorder. The development of a modified Autism Spectrum Rating Scale suitable for use in China is important for the identification of children in China with an autism spectrum disorder. In this study, we examined the Modified Chinese Autism Spectrum Rating Scale using a statistical technique known as Rasch analysis. Rasch analysis tests whether the questionnaire meets the standards for modern scientific measurement. We used Rasch analysis to examine data from 2013 children in China including 420 diagnosed with an autism spectrum disorder who had been rated by a parent or grandparent. After removing a small number of items (questions), the Modified Chinese Autism Spectrum Rating Scale met the stringent criteria for Rasch measurement. The availability of a reliable and precise tool for assessing behaviours characteristic of an autism spectrum disorder in Chinese children will improve the identification and diagnosis of autism spectrum disorder in China, thus enabling better provision of support services.

16.
Cancer Lett ; 511: 1-14, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-33894331

RESUMO

The excessive release of proinflammatory chemokines promotes cell proliferation and tumor growth in colorectal cancer. However, their regulatory functions and molecular pathogenesis have not been well elucidated. Here, we observed the upregulation of chemokine (C-X-C motif) ligand 13 (CXCL13) in human colorectal cancers and mouse intestinal tumors. Both CXCL13 deficiency and blockade of CXCL13 signaling ameliorated disease progression. CXCL13 promoted intestinal tumorigenesis through the activation of the AKT signaling pathway in a C-X-C chemokine receptor type 5 (CXCR5)-dependent manner. Intestinal microbiota translocation drove CXCL13 production in dendritic cells through the activation of NF-κB signaling. Inhibition of microbiota translocation decreased CXCL13 production and ameliorated intestinal tumorigenesis. Together, the results of this study identify a role for the CXCL13-CXCR5 axis is involved in the crosstalk between chemokines and cell growth during the development of intestinal tumorigenesis, which also provides a therapeutic strategy for targeting CXCL13/CXCR5 in the future clinical treatment of intestinal tumors.

17.
Nat Cell Biol ; 23(4): 424-436, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33820973

RESUMO

Although high-throughput RNA sequencing (RNA-seq) has greatly advanced small non-coding RNA (sncRNA) discovery, the currently widely used complementary DNA library construction protocol generates biased sequencing results. This is partially due to RNA modifications that interfere with adapter ligation and reverse transcription processes, which prevent the detection of sncRNAs bearing these modifications. Here, we present PANDORA-seq (panoramic RNA display by overcoming RNA modification aborted sequencing), employing a combinatorial enzymatic treatment to remove key RNA modifications that block adapter ligation and reverse transcription. PANDORA-seq identified abundant modified sncRNAs-mostly transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs)-that were previously undetected, exhibiting tissue-specific expression across mouse brain, liver, spleen and sperm, as well as cell-specific expression across embryonic stem cells (ESCs) and HeLa cells. Using PANDORA-seq, we revealed unprecedented landscapes of microRNA, tsRNA and rsRNA dynamics during the generation of induced pluripotent stem cells. Importantly, tsRNAs and rsRNAs that are downregulated during somatic cell reprogramming impact cellular translation in ESCs, suggesting a role in lineage differentiation.

18.
Food Chem ; 356: 129657, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33836359

RESUMO

Subgroups of starch granules from five maize phenotypes including waxy-, normal-, popcorn-, sweet corn- and high-amylose maize were sorted by flow cytometry (FC) utilizing the side scatter channel (SSC) and forward scatter channel (FSC). SSC and FSC mainly reflecting internal object complexity, and object size, respectively. Subgroups with higher FSC signal always showed higher SSC signal, indicating larger granules exhibited higher internal structural complexity. Wide-angle and small-angle X-ray scattering analysis showed that the subgroups showing high SSC signal intensity also had high lamellar scattering intensity, and low crystallinity. Vibrational transitions of bonds analyzed by Fourier Transform Infrared Spectroscopy (FT-IR) showed that the subgroups of maize starches, except sweet corn starch, with high SSC signal had high intensities at 1045 and 1022 cm-1. Hence, our data demonstrate that the structural complexity detected by the SSC signal is mainly associated with lamellar and crystalline features of starch granules.


Assuntos
Citometria de Fluxo/métodos , Amido/química , Zea mays/metabolismo , Amilopectina/química , Amilose/química , Espalhamento de Radiação , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
19.
Oncogene ; 40(20): 3533-3547, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33927351

RESUMO

Ferroptosis, a form of regulated cell death triggered by lipid peroxidation, was recently identified as an important mechanism in radiotherapy (RT)-mediated tumor suppression and radioresistance, although the exact genetic contexts in which to target ferroptosis in RT remains to be defined. p53 is the most commonly mutated gene in human cancers and a major effector to RT. Here, we identify ferroptosis as a critical mechanism to mediate p53 function in tumor radiosensitivity. Mechanistically, RT-mediated p53 activation antagonizes RT-induced SLC7A11 expression and represses glutathione synthesis, thereby promoting RT-induced lipid peroxidation and ferroptosis. p53 deficiency promotes radioresistance in cancer cells or tumors at least partly through SLC7A11-mediated ferroptosis inhibition. Ferroptosis inducers (FINs) that inhibit SLC7A11 exert significant radiosensitizing effects in tumor organoids and patient-derived xenografts with p53 mutation or deficiency. Finally, we show that RT-induced ferroptosis correlates with p53 activation and better clinical outcomes to RT in cancer patients. Together, our study uncovers a previously unappreciated role of ferroptosis in p53-mediated radiosensitization and suggest using FINs in combination with RT to treat p53-mutant cancers.

20.
Ann Hematol ; 100(6): 1509-1516, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33900450

RESUMO

Treatment outcomes of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) are far from satisfactory. Certain efficacy of ibrutinib has been observed in non-GCB subtype DLBCL patients. This study aimed to investigate the efficacy and safety of ibrutinib plus BCL2 inhibitor venetoclax in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression. Combinational therapy (ibrutinib 560mg/day; venetoclax started 1 week later, oral dose increased from 100 to 400mg/day in 3 weeks) was conducted, and one cycle was 4 weeks. Both drugs were stopped when disease progress or serious adverse reactions appear. The primary end-point was overall response rate (ORR) at two cycles. From December 2018 to July 2020, a total of 13 patients were treated with the combined therapy. Among them, eleven (84.6%) patients previously received at least two treatment regimens, eight (61.5%) patients were C-myc and BCL2 double expression. The ORR at two cycles was 61.5%, with 3 (23.1%) patients achieved complete remission (CR) and 5 (38.4%) patients achieved partial remission (PR). The ORR at four cycles and six cycles was 53.8% and 46.2%, respectively. The median duration of response was 11 months (range, 1.5-13.6 months). The median progression-free survival and overall survival were 5.6 months (range, 0.4-15.6) and 11.3 months (range, 2.8-17.2), respectively. The most common adverse event was grade 1/2 neutropenia (53.8%), and nonhematologic toxicities included Grade1/2 diarrhea (46.2%) and elevated liver enzymes (30.8%). Combined therapy of ibrutinib and venetoclax showed promising efficacy and synergistic effects in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression, and the toxicities were well-tolerated.


Assuntos
Adenina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Piperidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/induzido quimicamente , Piperidinas/efeitos adversos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Sulfonamidas/efeitos adversos , Resultado do Tratamento
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