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•Sonication-induced changes of albumins from Moringa oleifera seed (MOWP) was explored.•Changes in the secondary and tertiary structure of MOWP was observable.•The MOWP was aggregated ...but not significantly degraded by ultrasound.•Ultrasonic treatment could effectively improve the thermal stability of MOWP.•Solubility, foaming and emulsifying properties of MOWP were improvement by sonication.
Effect of ultrasonic power on the structure and functional properties of water-soluble protein extracted from defatted Moringa oleifera seed were explored. The results showed that ultrasonic treatment could reduce β-sheet and β-turn content of water-soluble protein from Moringa oleifera seed (MOWP) and increase the content of random coil and α-helix. Changes in intrinsic fluorescence spectra, surface hydrophobicity (H0) and thermal behaviors indicated that ultrasonic had significant effect on the tertiary structure of MOWP. The results of SEM and SDS-PAGE showed that the MOWP was aggregated but not significantly degraded by ultrasound. The solubility, foaming properties and emulsifying properties of MOWP increased firstly and then decreased with the increase of ultrasonic power. Ultrasonic treatment altered the functional properties of MOWP, which might be attributed to the exposure of hydrophilic group and the change of and secondary and tertiary structure.
Renal tubulointerstitial fibrosis was a crucial pathological feature of diabetic nephropathy (DN), and renal tubular injury might associate with abnormal mitophagy. In this study, we investigated the ...effects and molecular mechanisms of AMPK agonist metformin on mitophagy and cellular injury in renal tubular cell under diabetic condition. The high fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice model and HK-2 cells were used in this study. Metformin was administered in the drinking water (200 mg/kg/d) for 24 weeks. Renal tubulointerstitial lesions, oxidative stress and some indicators of mitophagy (e.g., LC3II, Pink1, and Parkin) were examined both in renal tissue and HK-2 cells. Additionally, compound C (an AMPK inhibitor) and Pink1 siRNA were applied to explore the molecular regulation mechanism of metformin on mitophagy. We found that the expression of p-AMPK, Pink1, Parkin, LC3II, and Atg5 in renal tissue of diabetic mice was decreased obviously. Metformin reduced the levels of serum creatinine, urine protein, and attenuated renal oxidative injury and fibrosis in HFD/STZ induced diabetic mice. In addition, Metformin reversed mitophagy dysfunction and the over-expression of NLRP3. In vitro pretreatment of HK-2 cells with AMPK inhibitor compound C or Pink1 siRNA negated the beneficial effects of metformin. Furthermore, we noted that metformin activated p-AMPK and promoted the translocation of Pink1 from the cytoplasm to mitochondria, then promoted the occurrence of mitophagy in HK-2 cells under HG/HFA ambience. Our results suggested for the first time that AMPK agonist metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice via activating mitophagy through a p-AMPK-Pink1-Parkin pathway.
ABSTRACT
Xanthomonas is a well-studied genus of bacterial plant pathogens whose members cause a variety of diseases in economically important crops worldwide. Genomic and functional studies of these ...phytopathogens have provided significant understanding of microbial-host interactions, bacterial virulence and host adaptation mechanisms including microbial ecology and epidemiology. In addition, several strains of Xanthomonas are important as producers of the extracellular polysaccharide, xanthan, used in the food and pharmaceutical industries. This polymer has also been implicated in several phases of the bacterial disease cycle. In this review, we summarise the current knowledge on the infection strategies and regulatory networks controlling virulence and adaptation mechanisms from Xanthomonas species and discuss the novel opportunities that this body of work has provided for disease control and plant health.
Here, we discuss the current knowledge surrounding regulatory networks and systems that control virulence and adaption mechanisms in Xanthomonas species. Additionally, we detail how study of these pathogens has provided novel opportunities for disease control and plant health.
Covalent organic frameworks (COFs) are one type of porous organic materials linked by covalent bonds. COFs materials exhibit many outstanding characteristics such as high porosity, high chemical and ...thermal stability, large specific surface area, efficient electron transfer efficiency, and the ability for predesigned structures. These exceptional advantages enable COFs materials to exhibit remarkable performance in photocatalysis. Additionally, the activity of COFs materials as photocatalysts can be significantly upgraded by ion doping and the formation of heterojunctions. This paper summarizes the latest research progress on COF‐based materials applied in photocatalytic systems. Initially, typical structures and preparation methods of COFs are analyzed and compared. Moreover, the essential principles of photocatalytic reactions over COFs‐based materials and the latest research developments in photocatalytic hydrogen production, CO2 reduction, pollutants elimination, organic transformation, and overall water splitting are indicated. At last, the outlook and challenges of COF‐based materials in photocatalysis are discussed. This review is intended to permit instructive guidance for the efficient use of photocatalysis based on COFs in the future.
In this review, typical structures and preparation methods of covalent organic framework (COFs) are introduced. Subsequently, the essential principles of photocatalytic reactions over COFs‐based materials and the latest research developments in photocatalytic hydrogen production, CO2 reduction, and pollutant elimination are discussed. Finally, challenges and prospects for COFs‐based materials applied in photocatalysis are proposed.
Purpose
Microvascular invasion (MVI) is a valuable predictor of survival in hepatocellular carcinoma (HCC) patients. This study developed predictive models using eXtreme Gradient Boosting (XGBoost) ...and deep learning based on CT images to predict MVI preoperatively.
Methods
In total, 405 patients were included. A total of 7302 radiomic features and 17 radiological features were extracted by a radiomics feature extraction package and radiologists, respectively. We developed a XGBoost model based on radiomics features, radiological features and clinical variables and a three-dimensional convolutional neural network (3D-CNN) to predict MVI status. Next, we compared the efficacy of the two models.
Results
Of the 405 patients, 220 (54.3%) were MVI positive, and 185 (45.7%) were MVI negative. The areas under the receiver operating characteristic curves (AUROCs) of the Radiomics-Radiological-Clinical (RRC) Model and 3D-CNN Model in the training set were 0.952 (95% confidence interval (CI) 0.923–0.973) and 0.980 (95% CI 0.959–0.993), respectively (
p
= 0.14). The AUROCs of the RRC Model and 3D-CNN Model in the validation set were 0.887 (95% CI 0.797–0.947) and 0.906 (95% CI 0.821–0.960), respectively (
p
= 0.83). Based on the MVI status predicted by the RRC and 3D-CNN Models, the mean recurrence-free survival (RFS) was significantly better in the predicted MVI-negative group than that in the predicted MVI-positive group (RRC Model: 69.95 vs. 24.80 months,
p
< 0.001; 3D-CNN Model: 64.06 vs. 31.05 months,
p
= 0.027).
Conclusion
The RRC Model and 3D-CNN models showed considerable efficacy in identifying MVI preoperatively. These machine learning models may facilitate decision-making in HCC treatment but requires further validation.
Inducing homologous-recombination (HR) deficiency is an effective strategy to broaden the indications of PARP inhibitors in the treatment of triple-negative breast cancer (TNBC). Herein, we find that ...repression of the oncogenic transcription factor FOXM1 using FOXM1 shRNA or FOXM1 inhibitor FDI-6 can sensitize BRCA-proficient TNBC to PARP inhibitor Olaparib in vitro and in vivo. Mechanistic studies show that Olaparib causes adaptive resistance by arresting the cell cycle at S and G
/M phases for HR repair, increasing the expression of CDK6, CCND1, CDK1, CCNA1, CCNB1, and CDC25B to promote cell cycle progression, and inducing the overexpression of FOXM1, PARP1/2, BRCA1/2, and Rad51 to activate precise repair of damaged DNA. FDI-6 inhibits the expression of FOXM1, PARP1/2, and genes involved in cell cycle control and DNA damage repair to sensitize TNBC cells to Olaparib by blocking cell cycle progression and DNA damage repair. Simultaneously targeting FOXM1 and PARP1/2 is an innovative therapy for more patients with TNBC.
All known riboswitches use their aptamer to senese one metabolite signal and their expression platform to regulate gene expression. Here, we characterize a SAM-I riboswitch (SAM-I
) from the ...Xanthomonas campestris that regulates methionine synthesis via the met operon. In vitro and in vivo experiments show that SAM-I
controls the met operon primarily at the translational level in response to cellular S-adenosylmethionine (SAM) levels. Biochemical and genetic data demonstrate that SAM-I
expression platform not only can repress gene expression in response to SAM binding to SAM-I
aptamer but also can sense and bind uncharged initiator Met tRNA, resulting in the sequestering of the anti-Shine-Dalgarno (SD) sequence and freeing the SD for translation initiation. These findings identify a SAM-I riboswitch with a dual functioning expression platform that regulates methionine synthesis through a previously unrecognized mechanism and discover a natural tRNA-sensing RNA element. This SAM-I riboswitch appears to be highly conserved in Xanthomonas species.
Pseudomonas aeruginosa, a significant opportunistic pathogen, can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) ...family. Sensing these signals leads to altered biofilm formation and increased tolerance to various antibiotics, and requires the histidine kinase PA1396. Here, we show that the membrane-associated sensory input domain of PA1396 has five transmembrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced auto-phosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds to develop novel adjuvants improving the efficacy of existing antibiotics.
Described herein is the enantioselective synthesis of Hantzsch‐type 1,4‐dihydropyridines (DHPs), which are frequently contained in pharmaceuticals. Readily available symmetrical 1,4‐DHPs were used as ...substrates, and the methyl group at the 2‐ or 6‐position of the 1,4‐DHP was selectively monobrominated by desymmetrizing enantioselective bromination. The inert C−H bond was converted into a versatile C−Br bond, which guaranteed the modification of the chiral 1,4‐DHP derivatives with high efficiency. Furthermore, axially chiral 4‐aryl pyridines were accessible by central‐to‐axial chirality conversion.
Readily available symmetrical 1,4‐dihydropyridines (1,4‐DHPs) were used as substrates to obtain chiral Hantzsch‐type 1,4‐DHPs, which are frequently contained in pharmaceuticals. The inert C−H bond was converted into a versatile C−Br bond, which enabled the modification of the chiral 1,4‐DHP derivatives with high efficiency by nucleophilic substitution. Furthermore, axially chiral 4‐aryl pyridines were accessible by central‐to‐axial chirality conversion.
Background
Acupuncture is commonly used for migraine prophylaxis; however, evidence of its efficacy was equivocal.
Aim
We aimed to evaluated the efficacy of acupuncture in migraine prophylaxis and ...calculated the required information size (RIS) to determine whether further clinical studies are required.
Methods
We searched Cochrane library, EMBASE and PubMed from inception to April 23th, 2020. Randomized trials that compared acupuncture with conventional drug therapy or sham acupuncture were included. The primary outcome was migraine episodes. Secondary outcomes were responder rate and adverse event.
Results
Twenty studies (
n
= 3380) met the inclusion criteria. When it comes to migraine episodes, Acupuncture was superior over sham acupuncture SMD = − 0.29, 95% CI (− 0.47 to − 0.11),
P
= 0.002 after treatment, while the difference between acupuncture and prophylactic drugs was not significant SMD = − 0.21, 95% CI (− 0.42 to 0.00),
P
= 0.06.Both TSA graphs indicated that more RCTs are needed. As for responder rate, the results after treatment showed that acupuncture was statistically significantly better than sham acupuncture RR 1.30, 95% CI (1.09–1.55),
P
= 0.003 as well as conventional drugs RR 1.24, 95% CI (1.04–1.48),
P
= 0.01. Both of their cumulative Z-curves intersected with the trial sequential monitoring boundaries favoring acupuncture. Compared to prophylactic medication, acupuncture can cause less adverse events RR 0.34, 95% CI (0.14–0.81),
P
= 0.01.
Conclusion
Acupuncture can reduce migraine episodes compared to sham one and can be an alternative and safe prophylactic treatment for conventional drugs therapy, but it should be further verified through more RCTs. Available studies suggested acupuncture was superior to sham acupuncture and conventional drugs in terms of responder rate as verified by TSA.
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