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1.
Front Plant Sci ; 12: 751398, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721479

RESUMO

Wheat stem (or black) rust is one of the most devastating fungal diseases, threatening global wheat production. Identification, mapping, and deployment of effective resistance genes are critical to addressing this challenge. In this study, we mapped and characterized one stem rust resistance (Sr) gene from the tetraploid durum wheat variety Kronos (temporary designation SrKN). This gene was mapped on the long arm of chromosome 2B and confers resistance to multiple virulent Pgt races, such as TRTTF and BCCBC. Using a large mapping population (3,366 gametes), we mapped SrKN within a 0.29 cM region flanked by the sequenced-based markers pku4856F2R2 and pku4917F3R3, which corresponds to 5.6- and 7.2-Mb regions in the Svevo and Chinese Spring reference genomes, respectively. Both regions include a cluster of nucleotide binding leucine-repeat (NLR) genes that likely includes the candidate gene. An allelism test failed to detect recombination between SrKN and the previously mapped Sr9e gene. This result, together with the similar seedling resistance responses and resistance profiles, suggested that SrKN and Sr9e may represent the same gene. We introgressed SrKN into common wheat and developed completely linked markers to accelerate its deployment in the wheat breeding programs. SrKN can be a valuable component of transgenic cassettes or gene pyramids that includes multiple resistance genes to control this devastating disease.

2.
Genes (Basel) ; 12(11)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34828258

RESUMO

Trehalose-6-phosphate phosphatase (TPP) genes take part in trehalose metabolism and also in stress tolerance, which has been well documented in many species but poorly understood in wheat. The present research has identified a family of 31 TPP genes in Triticum aestivum L. through homology searches and classified them into five clades by phylogenetic tree analysis, providing evidence of an evolutionary status with Hordeum vulgare, Brachypodium distachyon and Oryza sativa. The exon-intron distribution revealed a discrete evolutionary history and projected possible gene duplication occurrences. Furthermore, different computational approaches were used to analyze the physical and chemical properties, conserved domains and motifs, subcellular and chromosomal localization, and three-dimensional (3-D) protein structures. Cis-regulatory elements (CREs) analysis predicted that TaTPP promoters consist of CREs related to plant growth and development, hormones, and stress. Transcriptional analysis revealed that the transcription levels of TaTPPs were variable in different developmental stages and organs. In addition, qRT-PCR analysis showed that different TaTPPs were induced under salt and drought stresses and during leaf senescence. Therefore, the findings of the present study give fundamental genomic information and possible biological functions of the TaTPP gene family in wheat and will provide the path for a better understanding of TaTPPs involvement in wheat developmental processes, stress tolerance, and leaf senescence.

3.
J Nat Prod ; 84(11): 2953-2960, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34787427

RESUMO

Penicisteckins A-D (1-4), two pairs of atropodiastereomeric biaryl-type hetero- and homodimeric bis-isochromans with 7,5'- and 7,7'-linkages and a pair of atropodiastereomeric 2-(isochroman-5-yl)-1,4-benzoquinone derivatives [penicisteckins E (5) and F (6)], were isolated from the Penicillium steckii HNNU-5B18. Their structures including the absolute configuration were determined by extensive spectroscopic and single-crystal X-ray diffraction analysis and TDDFT-ECD calculations. Both the bis-isochromans and the isochroman/1,4-benzoquinone conjugates represent novel biaryl scaffolds containing both central and axial chirality elements. The monomer anserinone B (8) exhibited potent antibacterial activities against Staphylococcus aureus ATCC 29213 and methicillin-resistant Staphylococcus aureus with minimal inhibition concentration values ranging from 2 to 8 µg mL-1. Plausible biosynthetic pathways of 1-6 are proposed, which suggest how the absolute configurations of the isolates were established during the biosynthetic scheme.

4.
Cell Mol Immunol ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782757

RESUMO

Irreversible electroporation (IRE) is a new cancer ablation technology, but methods to improve IRE-induced therapeutic immunity are only beginning to be investigated. We developed a mouse model bearing large primary (300 mm3) and medium distant (100 mm3) EG7 lymphomas engineered to express ovalbumin (OVA) as a nominal tumor antigen. We established experimental protocols including IRE alone and IRE combined with Toll-like receptor (TLR)3/9 agonists (poly I:C/CpG) (IRE + pIC/CpG), PD-1 blockade (IRE + PD-1 blockade), or both (IRE + Combo) to investigate therapeutic effects on primary and distant EG7 tumors and conversion-promoting effects on the immunotolerant tumor microenvironment (TME). We demonstrated that IRE alone simulated very weak OVA-specific CD8+ T cell responses and did not inhibit primary tumor growth. IRE + pIC/CpG synergistically stimulated more efficient OVA-specific CD8+ T cell responses and primary tumor growth inhibition than IRE + PD-1 blockade. IRE + pIC/CpG played a major role in the modulation of immune cell profiles but a minor role in the downregulation of PD-L1 expression in the TME and vice versa for IRE + PD-1 blockade. IRE + Combo cooperatively induced potent OVA-specific CD8+ T cell immunity and rescued exhausted intratumoral CD8+ T cells, leading to eradication of not only primary tumors but also untreated concomitant distant tumors and lung metastases. IRE + Combo efficiently modulated immune cell profiles, as evidenced by reductions in immunotolerant type-2 (M2) macrophages, myeloid-derived suppressor-cells, plasmacytoid dendritic cells, and regulatory T cells and by increases in immunogenic M1 macrophages, CD169+ macrophages, type-1 conventional dendritic cells, and CD8+ T cells, leading to conversion of immunotolerance in not only primary TMEs but also untreated distant TMEs. IRE + Combo also showed effective therapeutic effects in two breast cancer models. Therefore, our results suggest that IRE + Combo is a promising strategy to improve IRE ablation therapy in cancer.

5.
Front Cardiovasc Med ; 8: 758158, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778410

RESUMO

Aims: The pathogenesis of diabetic cardiomyopathy (DCM) is complex and the detailed mechanism remains unclear. Coagulation protease activated Protein C (aPC) has been reported to have a protective effect in diabetic microvascular disease. Here, we investigated whether aPC could play a protective role in the occurrence and development of major diabetic complication DCM, and its underlying molecular mechanism. Methods and Results: In a mouse model of streptozotocin (STZ) induced DCM, endogenous aPC levels were reduced. Restoring aPC levels by exogenous administration of zymogen protein C (PC) improved cardiac function of diabetic mice measured by echocardiography and invasive hemodynamics. The cytoprotective effect of aPC in DCM is mediated by transcription factor Y-box binding protein-1 (YB-1). Mechanistically, MEF2B lies downstream of YB-1 and YB-1/MEF2B interaction restrains deleterious MEF2B promoter activity in DCM. The regulation of YB-1 on MEF2B transcription was analyzed by dual-luciferase and chromatin immunoprecipitation assays. In diabetic mice, aPC ameliorated YB-1 degradation via reducing its K48 ubiquitination through deubiquitinating enzyme otubain-1 (OTUB1) and improving the interaction between YB-1 and OTUB1. Using specific agonists and blocking antibodies, PAR1 and EPCR were identified as crucial receptors for aPC's dependent cytoprotective signaling. Conclusion: These data identify that the cytoprotective aPC signaling via PAR1/EPCR maintains YB-1 levels by preventing the ubiquitination and subsequent proteasomal degradation of YB-1 via OTUB1. By suppressing MEF2B transcription, YB-1 can protect against DCM. Collectively, the current study uncovered the important role of OTUB1/YB-1/MEF2B axis in DCM and targeting this pathway might offer a new therapeutic strategy for DCM. Translational Perspective: DCM is emerging at epidemic rate recently and the underlying mechanism remains unclear. This study explored the protective cell signaling mechanisms of aPC in mouse models of DCM. As a former FDA approved anti-sepsis drug, aPC along with its derivatives can be applied from bench to bed and can be explored as a new strategy for personalized treatment for DCM. Mechanistically, OTUB1/YB-1/MEF2B axis plays a critical role in the occurrence and development of DCM and offers a potential avenue for therapeutic targeting of DCM.

6.
Inorg Chem ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34784481

RESUMO

Broadband high-efficiency luminescent materials have become a hot spot in lead-free perovskite research. There are relatively few broadband yellow-green phosphors with both ultraviolet and blue excitation ranges, which make them more suitable for phosphor-converted white LEDs. Through the ion-exchanged strategy, Cs2Hf1-xTexCl6 (CH1-xTxC) vacancy halide double perovskites were successfully prepared at room temperature. Using different excitation ranges of CH1-xTxC, two types of high-quality white LEDs are obtained. By combining density functional theory calculations and experiments, it is proved that this bright broadband yellow-green emission (photoluminescence quantum yield of 83.46%) is not only derived from the ion transitions of Te4+ but also exhibits the inherent characteristics of self-trapped exciton emission. Our results not only broaden the application fields of lead-free halide perovskites but also provide further insights into the luminescence mechanism.

7.
ACS Appl Mater Interfaces ; 13(45): 53610-53617, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34730323

RESUMO

Photothermal therapy (PTT) has inherent advantages in the treatment of hypoxic tumors due to its optically controlled selectivity on tumor ablation and oxygen-independent nature. The subcellular organelle-targeting capability and photothermal conversion efficiency (PCE) at near-infrared (NIR) wavelength are the key parameters in the assessment of the photothermal agent (PTA). Here, we report that carbon dots (CDs) prepared by the hydrothermal treatment of coronene derivatives show a high PCE of 54.7% at 808 nm, which can be attributed to the narrow band gap and the presence of amounts of continuous energy bands on CDs. Moreover, the vibrations in the layered graphite structures of the CDs also increase the rate of nonradiative transition and thus enhance the PCE. Furthermore, the CDs also possess excellent photostability, biocompatibility, and cell penetration capability and could mainly accumulate in the lysosomes. These experiment results have proved that the CDs are suitable as an efficient NIR light-triggered PTA for efficient PTT against cancer.

8.
Nat Chem Biol ; 17(12): 1305-1313, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34725510

RESUMO

Triacsins are an intriguing class of specialized metabolites possessing a conserved N-hydroxytriazene moiety not found in any other known natural products. Triacsins are notable as potent acyl-CoA synthetase inhibitors in lipid metabolism, yet their biosynthesis has remained elusive. Through extensive mutagenesis and biochemical studies, we here report all enzymes required to construct and install the N-hydroxytriazene pharmacophore of triacsins. Two distinct ATP-dependent enzymes were revealed to catalyze the two consecutive N-N bond formation reactions, including a glycine-utilizing, hydrazine-forming enzyme (Tri28) and a nitrite-utilizing, N-nitrosating enzyme (Tri17). This study paves the way for future mechanistic interrogation and biocatalytic application of enzymes for N-N bond formation.

9.
Arch Insect Biochem Physiol ; 108(4): e21850, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34750851

RESUMO

Detoxification enzymes are necessary for insects to metabolize toxic substances and maintain physiological activities. Cytochromes P450 (CYPs), glutathione S-transferases (GSTs), and carboxylesterase (CarEs) are the main detoxification enzymes in insects. In addition, UDP-glucosyltransferase and ATP-binding cassette transporter also participate in the process of material metabolism. This study collected proteins related to detoxification in the silkworm, Bombyx mori (Lepidoptera: Bombycidae). And we performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on these proteins to understand their biological function. We constructed the protein-protein interaction network for the silkworm's detoxification enzymes and analyzed the network's topological properties. We found that BGIBMGA014046-TA, BGIBMGA003221-TA, BGIBMGA011092-TA, BGIBMGA000074-TA, and LOC732976 are the essential proteins in the network. These proteins are primarily involved in the process of ribosome biogenesis and may be related to protein synthesis. We integrated GO, KEGG, and network analysis and found that ribosome-associated protein and GSTs played a vital role in the detoxification process.


Assuntos
Bombyx , Sistema Enzimático do Citocromo P-450 , Glutationa Transferase/metabolismo , Mapas de Interação de Proteínas , Animais , Bombyx/genética , Bombyx/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Perfilação da Expressão Gênica , Ontologia Genética , Glutationa Transferase/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo
10.
BMC Infect Dis ; 21(1): 1137, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34742247

RESUMO

BACKGROUND: Liposuction is one of the most commonly performed aesthetic procedures. Toxic shock syndrome(TSS) is a rare, life-threatening complication. The incidence rate of TSS is very low in the plastic surgery field, especially after liposuction and fat transfer. CASE PRESENTATION: A 23-year-old female patient was transferred to our emergency department from an aesthetic clinic with sepsis shock features after received liposuction and fat transfer. The patient underwent TSS, disseminated intravascular coagulation(DIC), multiple organ dysfunction syndrome (MODS), symmetrical peripheral gangrene (SPG), and necrotizing soft tissue infection of the buttocks in the next 10 days. Authors used a series of debridement and reconstructive surgery including vacuum sealing drainage (VSD) treatment, artificial dermis grafts,split-thickness skin grafts, amputation surgeries when her vital signs were stable. The patient experienced desquamation of the hand on the 26th day. The skin grafts survived and the function of both fingers and toes recovered. She was discharged 2 months after admission and was in good health. CONCLUSION: TSS is extremely rare in the field of liposuction and autologous fat transfer. The mortality rate of TSS is very high. Early diagnosis and operative treatment, as well as correction of systemic abnormalities, are the important keys to save a patient's life.


Assuntos
Coagulação Intravascular Disseminada , Lipectomia , Choque Séptico , Adulto , Feminino , Gangrena/etiologia , Mãos , Humanos , Lipectomia/efeitos adversos , Choque Séptico/etiologia , Adulto Jovem
11.
Nanotechnology ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34768241

RESUMO

The MnO/C composites were obtained by co-precipitation method, which used Mn3O4 nanomaterials as precursors and dopamine solution after ultrasonic mixing and calcination under N2 atmosphere at different temperatures. By studying the difference of MnO/C nanomaterials formed at different temperatures, it was found that with the increase of calcination temperature, the materials appear obvious agglomeration. The optimal calcination temperature is 400 °C, and the resulting MnO/C is a uniformly dispersed slender nanowire structure. The specific capacitance of MnO/C nanowires can reach 356 F g-1 at 1 A g-1. In the meantime, the initial capacitance of MnO/C nanowires remains 106% after 5000 cycles. Moreover, the asymmetric supercapacitor (ASC) was installed, which displays a tremendous energy density of 30.944 Wh kg-1 along with a high power density of 10 kW kg-1. The composite material reveals a promising prospect in the application of supercapacitors.

12.
Front Pharmacol ; 12: 707399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603021

RESUMO

Energic deficiency of cardiomyocytes is a dominant cause of heart failure. An antianginal agent, trimetazidine improves the myocardial energetic supply. We presumed that trimetazidine protects the cardiomyocytes from the pressure overload-induced heart failure through improving the myocardial metabolism. C57BL/6 mice were subjected to transverse aortic constriction (TAC). After 4 weeks of TAC, heart failure was observed in mice manifested by an increased left ventricular (LV) chamber dimension, an impaired LV ejection fraction evaluated by echocardiography analysis, which were significantly restrained by the treatment of trimetazidine. Trimetazidine restored the mitochondrial morphology and function tested by cardiac transmission electron microscope and mitochondrial dynamic proteins analysis. Positron emission tomography showed that trimetazidine significantly elevated the glucose uptake in TAC mouse heart. Trimetazidine restrained the impairments of the insulin signaling in TAC mice and promoted the translocation of glucose transporter type IV (GLUT4) from the storage vesicle to membrane. However, these cardioprotective effects of trimetazidine in TAC mice were notably abolished by compound C (C.C), a specific AMPK inhibitor. The enlargement of neonatal rat cardiomyocyte induced by mechanical stretch, together with the increased expression of hypertrophy-associated proteins, mitochondria deformation and dysfunction were significantly ameliorated by trimetazidine. Trimetazidine enhanced the isolated cardiomyocyte glucose uptake in vitro. These benefits brought by trimetazidine were also removed with the presence of C.C. In conclusion, trimetazidine attenuated pressure overload-induced heart failure through improving myocardial mitochondrial function and glucose uptake via AMPK.

13.
Front Endocrinol (Lausanne) ; 12: 705154, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616362

RESUMO

Background: Diabetic cardiomyopathy (DbCM) is characterized by initial impairment of left ventricular relaxation followed by contractile dysfunction. Despite intensive research, the exact mechanism remains so far unsolved. Methods: We constructed weighted gene co-expression network analysis (WGCNA) to screen gene modules that were closely related with DbCM based on the GSE5606 dataset, which contained expression data of the cardiac left ventricle in a rodent model of streptozotocin (STZ)-induced DbCM. Then, the most related hub gene, angiopoietin-like 4 (ANGPTL4), was selected for functional ex vivo and in vitro assays. In our experiments, STZ-induced diabetic mice (C57BL/6J) and human cardiomyocytes (AC16) were used to study the functional roles and potential mechanisms of ANGPTL4 in DbCM. Results: WGCNA analysis revealed the yellow and green modules were most correlated with DbCM, and identified ANGPTL4 as one of the most significantly upregulated hub genes (ANGPTL4, ACOT1, DECR1, HMGCS2, and PDK4). Consistent with the bioinformatic analysis, the amount of ANGPTL4 was significantly upregulated in diabetic mouse heart. DbCM group, compared with the control group, had increased phosphorylation of focal adhesion kinase (FAK), reduced SIRT3 expression, increased SOD2 acetylation, upregulated NADPH oxidase activation, elevated reactive oxygen species (ROS) produciton, and enhanced apoptosis in the diabetic mouse heart. Moreover, ANGPTL4 induced apoptosis via FAK/SIRT3/ROS pathway in human cardiomyocytes (AC16) under high glucose condition in vitro.These effects were abrogated by treatment of two independent siRNA for ANGPTL4, whereas exogenous recombinant ANGPLT4 protein treatment exacerbated those effects in AC16. Conclusion: We found ANGPTL4, ACOT1, DECR1, HMGCS2, and PDK4 were significantly increased in diabetic heart. ANGPTL4 could promote cardiac apoptosis via a FAK/SIRT3/ROS dependent signaling pathway in DbCM.

14.
Front Cell Dev Biol ; 9: 656780, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621735

RESUMO

Objectives: The purpose of this study is to investigate the effects of transplantation of microencapsulated neural stem cells (MC-NSCs), which downregulate the P2 × 4 receptor (P2 × 4R) overexpression and relieve neuropathic pain (NPP). Methods: Neural stem cells (NSCs) and MC-NSCs were transplanted to the injured sciatic nerve. Transmission electron microscope and immunofluorescence were used to observe the changes of injured sciatic nerve. Behavioral methods were used to detect mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) of rats. Expression levels of P2 × 4Rs and p-p65 in the spinal cord segment of rats were measured by using molecular biology methods. The concentrations of IL-1ß and TNF-α were detected in serum of rats by ELISA. Results: After sciatic nerve injury, the sciatic nerve fibers had the myelinated lamina separated, and disintegrated fragments could be seen. The fluorescence intensity of myelin MBP was weakened. The MWT and TWL were significantly decreased, the expression of P2 × 4Rs and p-p65 were significantly increased, and the concentrations of IL-1ß and TNF-α were increased. After NSC and MC-NSC transplantation, the myelin sheath of the sciatic nerve was relatively intact, some demyelination changes could be seen, and the injured sciatic nerve has been improved. The fluorescence intensity of myelin MBP was increased. The MWT and TWL were increased, expression levels of P2 × 4Rs and p-p65 were decreased, and the concentrations of IL-1ß and TNF-α were significantly decreased. Compared with NSC transplantation, transplantation of MC-NSCs could better repair the damaged sciatic nerve, decrease the expression of P2 × 4Rs and p-p65, decrease the level of IL-1ß and TNF-α, and relieve pain (all p-values < 0.05). Conclusion: NSCs and MC-NSCs transplantation may alleviate pain by reducing the expression of P2 × 4Rs and inhibiting the activation of NF-KB signaling, while MC-NSCs transplantation has a better effect of suppressing pain. Our experimental results provide new data support for the treatment of NPP.

15.
ACS Omega ; 6(40): 26575-26582, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34661012

RESUMO

The design and synthesis of single-molecule amphiphilic and multifunctional phototherapeutic agents are important to cancer diagnosis and therapy. In this work, we developed three amphiphilic diketopyrrolopyrrole derivatives (TPADPP, DTPADPP, and TPADDPP) with different donor-acceptor structures and poly(ethylene glycol) side chains. The corresponding nanoparticles (NPs) were obtained via a self-assembly from three amphiphilic DPP derivatives and used as smart phototherapeutic agents for tumor diagnosis and treatment. The three amphiphilic DPP NPs exhibited near-infrared (NIR) emissions and good biocompatibility. Thus, they could be used as fluorescence (FL) imaging agents for guided therapy. DTPADPP NPs and TPADDPP NPs also displayed excellent photothermal performance and high accumulation in the tumor. Owing to these beneficial features, the DTPADPP NPs and TPADDPP NPs synthesized herein are suitable for NIR FL imaging and effective photothermal therapy against the tumor in vivo.

16.
Chem Commun (Camb) ; 57(83): 10943-10946, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34604883

RESUMO

Single matrix white luminescent materials are relatively rare. Here, we report an excitation wavelength-dependent Cs2HfCl6:xSb (CHC:xSb) vacancy-ordered double perovskite where, by adjusting the excitation wavelength, different types of white light emission can be obtained.

17.
Medicine (Baltimore) ; 100(40): e27476, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622877

RESUMO

BACKGROUND: Glucokinase activators (GKAs) are a novel family of glucose-lowering agents used for the treatment of type-2 diabetes mellitus. Treatment with different GKAs has been shown to reduce blood glucose levels in these patients. We compared the efficacy/safety of GKAs in patients with type-2 diabetes mellitus through a meta-analysis. METHODS: We searched the PubMed, Excerpt Medica Database, and Cochrane Central Register of Controlled Trials databases for articles published before December 30, 2020. We computed the weighted mean difference (WMD) and 95% confidence interval (CI) for the change from baseline to the study endpoint for GKA versus placebo treatments. RESULTS: A total of 4 articles (5 studies) were included in the meta-analysis. GKAs were associated with reductions in glycated hemoglobin levels from baseline (WMD, -0.3%; 95% CI, -0.466% to -0.134%). No significant difference between GKA and placebo treatment was observed in the results of fasting plasma glucose levels from baseline (WMD 0.013 mmol/L; 95% CI, -0.304-0.33 mmol/L). A significantly higher change in 2-hour postprandial plasma glucose (2-h PPG) levels (WMD -2.434 mmol/L; 95% CI, -3.304 to -1.564 mmol/L) was observed following GKA than placebo treatment. GKAs were associated with a higher prevalence of causing hypoglycemic events than placebo treatment (risk difference [RD], 0.06; 95% CI 0.013-0.106). GKAs had no association with the risk of developing adverse effects (RD, 0.038; 95% CI, -0.03-0.106) and serious adverse events (RD, 0.01; 95% CI, -0.004-0.023). CONCLUSIONS: GKAs were more effective for postprandial blood glucose control. However, these agents showed a significantly high risk of causing hypoglycemia. PROSPERO REGISTRATION NUMBER: CRD42021220364.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucoquinase/biossíntese , Hipoglicemiantes/uso terapêutico , Glicemia , Hemoglobina A Glicada , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Período Pós-Prandial , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Org Biomol Chem ; 19(41): 8940-8946, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34617948

RESUMO

Berninamycins are a class of thiopeptide antibiotics with potent activity against Gram-positive bacteria. Heterologous expression of the berninamycin (ber) biosynthetic gene cluster from marine-derived Streptomyces sp. SCSIO 11878 in different terrestrial model Streptomyces hosts led to the production of berninamycins A (1) and B (2) in Streptomyces lividans SBT18 and Streptomyces coelicolor M1154, while two new linearized berninamycins J (3) and K (4) were obtained in Streptomyces albus J1074. Their structures were elucidated by detailed interpretation of NMR data and Marfey's method. Bioactivity assays showed that the linear thiopeptides 3 and 4 were less potent than 1 and 2 in antibacterial activity. This work indicates that undefined host-dependent enzymes might be responsible for generating the linear thiopeptides 3 and 4 in S. albus J1074.

19.
Plant Biotechnol J ; 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34695276

RESUMO

Wheat stem (or black) rust, caused by Puccinia graminis f. sp. tritici (Pgt), has been historically among the most devastating global fungal diseases of wheat. The recent occurrence and spread of new virulent races such as Ug99 have prompted global efforts to identify and isolate more effective stem rust resistance (Sr) genes. Here, we report the map-based cloning of the Ug99-effective SrTm5 gene from diploid wheat Triticum monococcum accession PI 306540 that encodes a typical coiled-coil nucleotide-binding leucine-rich repeat protein. This gene, designated as Sr22b, is a new allele of Sr22 with a rare insertion of a large (13.8-kb) retrotransposon into its second intron. Biolistic transformation of an ˜112-kb circular bacterial artificial chromosome plasmid carrying Sr22b into the susceptible wheat variety Fielder was sufficient to confer resistance to stem rust. In a survey of 168 wheat genotypes, Sr22b was present only in cultivated T. monococcum subsp. monococcum accessions but absent in all tested tetraploid and hexaploid wheat lines. We developed a diagnostic molecular marker for Sr22b and successfully introgressed a T. monococcum chromosome segment containing this gene into hexaploid wheat to accelerate its deployment and pyramiding with other Sr genes in wheat breeding programmes. Sr22b can be a valuable component of gene pyramids or transgenic cassettes combining different resistance genes to control this devastating disease.

20.
Front Oncol ; 11: 713645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540681

RESUMO

Background: Partial nephrectomy (PN) is the recommended treatment for T1 renal cell carcinoma (RCC). Compared with suture PN, sutureless PN reduces the difficulty and time of operation, but the safety and feasibility have been controversial. This meta-analysis was conducted to compare the function and perioperative outcomes of suture and sutureless PN for T1 RCC. Methods: Systematic literature review was performed up to April 2021 using multiple databases to identify eligible comparative studies. According to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, identification and selection of the studies were conducted. Meta-analysis was performed for studies comparing suture to sutureless PN for both T1a and T1b RCC. In addition, subgroup analysis was performed on operation time, warm ischemia time, estimated blood loss, and postoperative complications. Sensitivity analysis was used in analysis with high heterogeneity (operation time and estimated blood loss). Results: Eight retrospective studies were included with a total of 1,156 patients; of the 1,156 patients, 499 received sutureless PN and 707 received suture PN. The results showed that sutureless PN had shorter operative time (I2 = 0%, P < 0.001), warm ischemia time (I2 = 97.5%, P < 0.001), and lower clamping rate (I2 = 85.8%, P = 0.003), but estimated blood loss (I2 = 76.6%, P = 0.064) had no difference. In the comparison of perioperative outcomes, there was no significant difference in postoperative complications (I2 = 0%, P = 0.999), positive surgical margins (I2 = 0%, P = 0.356), postoperative estimated glomerular filtration rat (eGFR) (I2 = 0%, P = 0.656), and tumor recurrence (I2 = 0%, P = 0.531). Conclusions: In T1a RCC with low RENAL score, sutureless PN is a feasible choice, whereas it should not be overestimated in T1b RCC.

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