The lack of reliable drugs is a therapeutic challenge of advanced breast cancers (ABCs). Resveratrol (Res) exerts inhibitory effects on breast cancer cell lines and animal models, while its efficacy ...against individual breast cancer cases remains unknown. This study aims to use ABC‐derived organoids (ABCOs) as the ex vivo therapeutic platform to clarify the effectiveness of resveratrol against different ABC subtypes. Immunohistochemical staining confirmed that the ABCOs maintained their original tumors' ER, PR, HER2, and Ki67 expression patterns. ABCO proliferation and viability tests showed >50% cell death rates in 79.2% (19/24) of Res‐treated, 28.6% (2/7) fulvestrant‐treated, 66.7% (4/6) paclitaxel‐treated, and 66.7% (6/9) gemcitabine‐treated ABCOs. pSTAT3 nuclear translocation was more frequent in Res‐sensitive (17/19; 89.47%) than that (1/5; 20%) of Res‐insensitive ABCOs, which were suppressed upon Res treatment. Statistical analysis revealed a close correlation of STAT3 activation with the efficacy of Res, but not related to tumor receptor expression patterns (ER, PR, HER2) and pathological classification. We demonstrate for the first time the higher efficacy and broader spectrum of Res against different subtypes of ABCOs in comparison with that of conventional antibreast cancer drugs, providing an alternative approach for better management of ABCs.
The petrogenesis and tectonic evolution of the Mesozoic ophiolitic mélanges in the western section of the Yarlung Zangbo suture zone (YZSZ) remain controversial. In this paper, we present the results ...of whole-rock geochemical and SrNd isotope analyses, zircon UPb ages and in situ LuHf isotopic data obtained from mafic rocks of the northern and southern sub-belts of the western YZSZ Mesozoic ophiolitic mélanges to help us understand these controversial issues. Diabases and dolerites from the northern sub-belt and gabbros from the southern sub-belt exhibit variable fore-arc basalt (FAB)-like geochemical compositions and have zircon UPb ages of ∼126.4–120.3 Ma. In addition, gabbro-diabases from the northern sub-belt have boninite series affinities and yield a zircon UPb age of ∼125.7 Ma. These results, along with previous studies on the YZSZ Mesozoic ophiolitic mélanges and the Gangdese arc, reveal that the western YZSZ Mesozoic ophiolites were likely generated over multiple stages in the epicontinental Gangdese fore-arc basin as the Yarlung Zangbo Neo-Tethyan Ocean subducted northward in front of the Lhasa terrane. The Early Cretaceous FAB-like and boninite series mafic rocks were formed by the reinitiation of subduction, which was followed by a retreat of the subduction zone and the creation of the fore-arc basin and strong hyperextension, accompanied by asthenosphere upwelling at ∼130–120 Ma. During this process, the upwelling asthenosphere underwent decompressional melting with limited penetration of slab-derived fluids and gave rise to the N-MORB (normal mid-ocean ridge basalt)-like basaltic magmas that intruded the overlying, previously generated depleted mantle as FAB-like gabbro, diabase and dolerite sills or dykes. Then, boninitic magmas represented by boninitic gabbro-diabases were generated by remelting the extremely depleted residual mantle source, which was metasomatized by a small amount of slab-derived fluids, following previous extractions of FAB-like magma.
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•The western YZSZ Mesozoic ophiolites contain FAB-like and boninitic mafic rocks.•These rocks formed in the Gangdese fore-arc basin during the Early Cretaceous.•The western YZSZ Mesozoic ophiolites have a multistage fore-arc extension model.
•In situ electrospinning combined with laparoscope for minimally invasive surgery.•Simultaneously achieve precise deposition without thickening fiber diameter.•Faster hemostasis than many other ...traditional laparoscopic hemostasis methods.•More rapid recovery rate after the hemostasis with laparoscopic electrospinning.
In situ deposition of nanofibers onto living organs could improve the adhesion between nanofiber membranes and organs and thus accelerate the hemostatic effect. Electrospinning is preferable over blow spinning for in situ hemostasis, as blow spinning may damage the wound because of the strong airflow and introduces a recoil phenomenon when the airflow encounters the organ that fibers would deposit onto the surrounding organs causing tissue adhesion. Minimally invasive surgery has increased recently and become the first choice for patients due to its minimal trauma and slight pain. Herein, we combine in situ electrospinning with minimally invasive surgery and show that electrospun nanofibers can be fabricated through the laparoscope and directly deposited onto the living organ. A cone converging structure was also introduced in this laparoscopic electrospinning, which can more precisely deposit nanofibers and decrease the deposition area of the nanofiber membrane without thickening the fiber diameter. During a minimally invasive surgery performed on pigs, this laparoscopic electrospinning technique exhibited rapid hemostasis, less postoperative inflammatory responses and faster recovery than traditional hemostasis methods. The hemostasis time of electrospinning method was approximately 5 s, which was faster than that of the suture group at 3 min and smear group at 14 s. The electrospun membrane thickness was approximately 300 μm, which was thinner than that of the smearing group at approximately 1 mm. The deposition area of the electrospun NOCA membrane can also be finely tuned by the cone converging structure and electrospinning distance, and it is superior to the smear method because the operation is performed through a long laparoscopic tube (~37 cm), which minimizes the effect of hand shaking on targeting the wound site.
Based on the perturbation formulae of the spin Hamiltonian parameters (SHPs) for a tetragonally compressed octahedral 3d
1
cluster, the defect structures and SHPs of V
4+
in strontium-tellurium ...borate ((30-x)SrO-xTeO
2
-10TiO
2
-58B
2
O
3
-2V
2
O
5
at distinct TeO
2
contents x = 1, 2, 3, 4 and 5 mol %) glasses are systematically investigated. The involved model quantities (i.e. covalent factor N, tetragonal compression ratio τ, core polarization constant κ and reduction factor H) at various x reasonably reproduce the experimental SHPs, and these quantities are further fitted with uniform Fourier-type content functions (FTCF) with merely three adjusted parameters. The different content fluctuations of these quantities are ascribed to content declines of the strong network modifier SrO and hence the modulations in local tetragonal compression, system compactness and electron cloud distribution near vanadium in the glass network.
Astrocytes activation in response to stroke results in altered mitochondrial exchange with neurons. Ginsenoside Rb1is a major ginsenoside of Panax ginseng particularly known for its neuroprotective ...potential. This work aimed to investigate if Rb1 could rescue neurons from ischemic insult via astrocyte inactivation and mitochondrial transfer. We prepared conditioned astrocytes-derived medium for co-culture with neurons and examined the role of Rb1 in mitochondrial transfer from astrocytes to neurons. The neuroprotective potential of Rb1 was further confirmed in vivo using a mouse model of brain ischemia. In response to oxygen-glucose deprivation and reperfusion (OGD/R), astrocytes were reactivated and produced reactive oxygen species (ROS), an action that was blocked by Rb1. Mechanistically, Rb1 inhibited NADH dehydrogenase in mitochondrial complex I to block reverse electron transport-derived ROS production from complex I, and thus inactivated astrocytes to protect the mitochondria. Mitochondrial signal, mitochondrial membrane potential and ATP production detected in conditioned astrocyte-derived medium indicated that Rb1 protected functional mitochondria and facilitated their transfer. When neurons were injured by OGD/R insult, co-culturing with conditioned medium increased mitochondrial membrane potential and oxygen consumption rate within the neurons, indicating the protection conferred on them by Rb1 via mitochondrial transfer from astrocytes. Using the ischemic mouse brain model, CD38 knockdown in the cerebral ventricles diminished the neuroprotective effects of Rb1, providing evidence in support of the role of astrocyte mitochondrial transfer. Transient inhibition of mitochondrial complex I by Rb1 reduced mitochondrial ROS production and consequently avoided astrocyte activation. Astrocyte mitochondrial transfer therefore seemed a means by which Rb1 could promote neuronal survival and function. Different from the neurocentric view, these findings suggest the astrocytes may be a promising target for pharmacological interventions in ischemic brain injury.
Two unique immunosensors made of aluminum-based metal-organic frameworks (MOFs), namely, 515- and 516-MOFs, with 4,4',4''-nitrilotribenzoic acid (H3NTB) were successfully obtained to efficiently ...assess food safety. The as-prepared 515- and 516-MOFs exhibited superior thermal and physicochemical stability, high electrochemical activity, and good biocompatibility. Among these immunosensors, 516-MOF showed a preferable biosensing ability toward analytes determined by electrochemical techniques. The developed 516-MOF-based electrochemical biosensor not only demonstrated high sensitivity with low detection limits of 0.70 and 0.40pgmL−1 toward vomitoxin and salbutamol, respectively, but also showed good selectivity in the presence of other interferences. Therefore, with the advantages of high sensitivity, good selectivity, and simple operation, this new strategy is believed to exhibit great potential for simple and convenient detection of poisonous and harmful residues in food.
•Two high-stable Al-MOF-based immunosensors were constructed.•High sensitivity and selectivity of the developed biosensor.•Ultra-sensitively detecting poisonous and harmful residues in food.
Alzheimer's disease (AD) is the most common cause of dementia among elderly population. Deranged β-amyloid (Aβ) trafficking across the blood-brain barrier is known to be a critical element in the ...pathogenesis of AD. In the vascular endothelial cells of hippocampus, Aβ transport is mainly mediated by low-density lipoprotein-associated protein 1 (LRP1) and the receptor for advanced glycation end (RAGE) products; therefore, LRP1 and RAGE endothelial cells are potential therapeutic targets for AD. In this study, we explored the effects of Formononetin (FMN) on learning and memory improvement in APP/PS1 mice and the related mechanisms. We found that FMN significantly improved learning and memory ability by suppressing Aβ production from APP processing, RAGE-dependent inflammatory signaling and promoted LRP1-dependent cerebral Aβ clearance pathway. Moreover, FMN treatment alleviated ultrastructural changes in hippocampal vascular endothelial cells. In conclusion, we believe that FMN may be an efficacious and promising treatment for AD.
Formononetin ameliorates learning and memory impairment in mouse model of Alzheimer's disease via suppressing inflammatory signaling and promoted Aβ clearance.
4,4′-Azobis (4-cyanovaleric acid) (ACVA) is known as a kind of water-soluble azo initiator which was widely used in the radical polymerization process. As same as other azo compounds, ACVA may also ...trigger thermal runaway accidents at high temperatures due to its specific –N=N– structure. To qualify its pyrolysis characteristics, thermogravimetric analysis and differential scanning calorimetry were applied to this investigation, moreover, the TGA-FTIR combination technology was used in the product analysis part. The results showed that ACVA has a complex decomposition process, there are four mass loss stages during its pyrolysis, the heat release mainly occurred in the first and final decomposition stage and the heat flux in the middle stages was very disordered. Different decomposition stages were accompanied by different decomposition products, and some of them were considered toxic, such as HCN and CH
4
. Thermokinetic parameters such as apparent activation energy (
E
a
) were also calculated in this paper by using Kissinger–Akahira–Sunose (KAS) method. Surprisingly, ACVA has the lowest
E
a
(91 kJ mol
−1
) and the highest heat release (4706 J g
−1
) compared with some commonly used azos, which means it will more easily suffer a serious runaway accident. All these studies can give us a comprehensive understanding of the thermal decomposition of ACVA to prevent accidents.
Interstitial lung disease (ILD) is the most widespread and fatal pulmonary complication of rheumatoid arthritis (RA). Existing knowledge on the prevalence and risk factors of rheumatoid ...arthritis-associated interstitial lung disease (RA-ILD) is inconclusive. Therefore, we designed this review to address this gap.
To find relevant observational studies discussing the prevalence and/or risk factors of RA-ILD, EMBASE, Web of Science, PubMed, and the Cochrane Library were explored. The pooled odds ratios (ORs) / hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with a fixed/ random effects model. While subgroup analysis, meta-regression analysis and sensitivity analysis were carried out to determine the sources of heterogeneity, the
statistic was utilized to assess between-studies heterogeneity. Funnel plots and Egger's test were employed to assess publication bias. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, our review was conducted.
A total of 56 studies with 11,851 RA-ILD patients were included in this meta-analysis. The pooled prevalence of RA-ILD was 18.7% (95% CI 15.8-21.6) with significant heterogeneity (
= 96.4%). The prevalence of RA-ILD was found to be more likely as a result of several identified factors, including male sex (ORs = 1.92 95% CI 1.70-2.16), older age (WMDs = 6.89, 95% CI 3.10-10.67), having a smoking history (ORs =1.91, 95% CI 1.48-2.47), pulmonary comorbidities predicted (HRs = 2.08, 95% CI 1.89-2.30), longer RA duration (ORs = 1.03, 95% CI 1.01-1.05), older age of RA onset (WMDs =4.46, 95% CI 0.63-8.29), positive RF (HRs = 1.15, 95%CI 0.75-1.77; ORs = 2.11, 95%CI 1.65-2.68), positive ACPA (ORs = 2.11, 95%CI 1.65-2.68), higher ESR (ORs = 1.008, 95%CI 1.002-1.014), moderate and high DAS28 (≥3.2) (ORs = 1.87, 95%CI 1.36-2.58), rheumatoid nodules (ORs = 1.87, 95% CI 1.18-2.98), LEF use (ORs = 1.42, 95%CI 1.08-1.87) and steroid use (HRs= 1.70, 1.13-2.55). The use of biological agents was a protective factor (HRs = 0.77, 95% CI 0.69-0.87).
The pooled prevalence of RA-ILD in our study was approximately 18.7%. Furthermore, we identified 13 risk factors for RA-ILD, including male sex, older age, having a smoking history, pulmonary comorbidities, older age of RA onset, longer RA duration, positive RF, positive ACPA, higher ESR, moderate and high DAS28 (≥3.2), rheumatoid nodules, LEF use and steroid use. Additionally, biological agents use was a protective factor.
Soil salinity is one of the serious environmental issues worldwide. In the present study, we made an attempt to isolate endophytic actinobacteria from halophyte and evaluate their growth promoting ...ability in Arabidopsis thaliana under salt stress through transcriptomic analysis. Two endophytic strains SYSU 333322 and SYSU 333140 were isolated and 16S rRNA gene sequence analysis suggests that these strains belong to Arthrobacter endophyticus and Nocardiopsis alba, respectively. To evaluate the growth promoting ability of two strains in Arabidopsis thaliana four experimental set up were designed. Set up designated s322 and s140 includes strains SYSU 333322 and SYSU 333140, respectively inoculated with A. thaliana under salt stress; set up designated MS322 and MS140 includes strains SYSU 333322 and SYSU 333140, respectively inoculated with A. thaliana without salt stress; MS includes seedlings without bacterial strains and salt stress; C150 includes seedlings grown in 150 mmol L−1NaCl. A. endophyticus strain SYSU 333322 and N. alba strain SYSU 333140 were efficient to promote A. thaliana growth under salt stress A. endophyticus strain SYSU 333322 was more efficient than N. alba strain SYSU 333140 for growth promotion. Although A. endophyticus strain SYSU 333322 and N. alba strain SYSU 333140 were isolated from the same host, their mechanism of growth promotion in A. thaliana under salt stress was different. Gene encoding for chlorophyll a reductase, peptide-methionine (R)-S-oxide reductase, and potassium ion uptake were up-regulated when A. thaliana inoculated with strain SYSU 333322 and SYSU 333140 under salt stress. Pathways such as carotenoid biosynthesis, phenylalanine metabolism, phenylpropanoid biosynthesis, glycerolipid metabolism, and nitrogen metabolism played a crucial role in enhancing the salt stress tolerance of A. thaliana. Our results suggest that different bacteria have a different mechanism to promote plant growth under salt stress and hence it is necessary to understand the mechanism to overcome soil salinity problem.
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•Arabidopsis thaliana growth enhancement under salt stress by endophytic actinobacteria•Arthrobacter endophyticus showed better growth enhancement than Nocardiopsis alba.•Increased chlorophyll content, root length, and biomass in Arabidopsis thaliana under salt stress
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