Cryptochrome 1b represses gibberellin signaling to enhance lodging resistance in maize.

Maize (Zea mays L.) is one of the most important crops worldwide. Photoperiod, light quality, and light intensity in the environment can affect the growth, development, yield, and quality of maize. In Arabidopsis (Arabidopsis thaliana), cryptochromes are blue-light receptors that mediate the photocontrol of stem elongation, leaf expansion, shade tolerance, and photoperiodic flowering. However, the function of maize cryptochrome ZmCRY in maize architecture and photomorphogenic development remains largely elusive. The ZmCRY1b transgene product can activate the light signaling pathway in Arabidopsis and complement the etiolation phenotype of the cry1-304 mutant. Our findings show that the loss-of-function mutant of ZmCRY1b in maize exhibits more etiolation phenotypes under low blue light and appears slender in the field compared with wild-type plants. Under blue and white light, overexpression of ZmCRY1b in maize substantially inhibits seedling etiolation and shade response by enhancing protein accumulation of the bZIP transcription factors ELONGATED HYPOCOTYL 5 (ZmHY5) and ELONGATED HYPOCOTYL 5-LIKE (ZmHY5L), which directly upregulate the expression of genes encoding gibberellin (GA) 2-oxidase to deactivate GA and repress plant height. More interestingly, ZmCRY1b enhances lodging resistance by reducing plant and ear heights and promoting root growth in both inbred lines and hybrids. In conclusion, ZmCRY1b contributes blue-light signaling upon seedling de-etiolation and integrates light signals with the GA metabolic pathway in maize, resulting in lodging resistance and providing information for improving maize varieties.

Light-accelerating oxidase-mimicking activity of black phosphorus quantum dots for colorimetric detection of acetylcholinesterase activity and inhibitor screening.

A feasible and sensitive colorimetric platform was established for the assay of acetylcholinesterase (AChE) activity and evaluation of its inhibitor screening, based upon the light-accelerating oxidase-mimicking activity of black phosphorus quantum dots (BP QDs). The BP QDs were synthesized through a thermal exfoliation method and characterized using various techniques. The BP QDs exhibit oxidase-mimicking catalytic activity on dissolved oxygen-mediating oxidation of 3,3',5,5'-tetramethylbenzidine, a typical substrate of oxidase. This results in a transformation of 3,3',5,5'-tetramethylbenzidine into its blue oxidized product, which has a visible absorption peak at 652 nm. The exposure of 365 nm light irradiation significantly accelerates the oxidase-mimicking activity of the BP QDs and speeds up the reaction efficiency. AChE can specifically catalyze the decomposition of its substrate acetylthiocholine chloride to thiocholine. Thiocholine has reducing capacity and can thus reduce the oxidase-mimicking activity of the BP QDs. As a result, the oxidation of 3,3',5,5'-tetramethylbenzidine is hindered and the blue solution becomes paler. This gives a linear response for AChE ranging from 0.5 to 10.0 mU mL-1 and a detection limit of 0.17 mU mL-1. The assay was successfully applied to evaluate inhibitor screening with neostigmine as the model.

A thermoreversible antibacterial zeolite-based nanoparticles loaded hydrogel promotes diabetic wound healing via detrimental factor neutralization and ROS scavenging.

BACKGROUND: As recovery time of diabetic wound injury is prolonged by the production of detrimental factors, including reactive oxygen species (ROS) and inflammatory cytokines, attenuating the oxidative stress and inflammatory reactions in the microenvironment of the diabetic wound site would be significant. EXPERIMENTAL DESIGN: In our study, we prepared thermoreversible, antibacterial zeolite-based nanoparticles loaded hydrogel to promote diabetic wound healing via the neutralization of detrimental factors such as inflammatory cytokines and ROS. RESULTS: The cerium (Ce)-doped biotype Linde type A (LTA) zeolite nanoparticles synergistically eliminated mitochondrial ROS and neutralized free inflammatory factors, thus remodeling the anti-inflammatory microenvironment of the wound and enhancing angiogenesis. Moreover, the thermoreversible hydrogel composed of Pluronic F127 and chitosan demonstrated strong haemostatic and bactericidal behavior. CONCLUSIONS: In conclusion, the obtained thermoreversible, antibacterial, zeolite-based nanoparticles loaded hydrogels represent a multi-targeted combination therapy for diabetic wound healing.

Nurses' core emergency competencies for COVID-19 in China: A cross-sectional study.

AIM: To investigate nurses' core emergency competencies for handling the coronavirus disease-19 (COVID-19) and analyse the factors associated with those competencies. BACKGROUND: COVID-19 has become a major global public health event. Nursing staff have played an important role in COVID-19 prevention and control. Understanding their emergency competencies for handling COVID-19, and the potential disadvantages will help governments to develop targeted training policies and improve nurses' capacities in relation to pandemics and emergency preparedness. INTRODUCTION: COVID-19 is a disastrous infectious disease, but the competencies of nurses in China to handle COVID-19 have not been well documented. METHODS: We conducted a cross-sectional survey on nurses from 22 provinces of China in February 2020. The scores of self-report questionnaires were used to analyse their competencies for core emergency care, and linear regression analysis was used to explore influential factors. RESULTS: A total of 2570 nurses participated. The study revealed that nurses had a good grasp of COVID-19 knowledge, but the majority of nurses lacked experience in isolation ward work and emergency training. We found that age, professional title, work department, major work content, total work time, disaster rescue history, emergency training and infectious disease training were associated with core emergency competencies. CONCLUSIONS: Chinese nurses were qualified for handling COVID-19 but still need to strengthen the accumulation of practical experience. IMPLICATIONS FOR NURSING: Nurses should actively participate in emergencies to strengthen their operational capacity, whether in training or actual practice. IMPLICATIONS FOR NURSING/HEALTH POLICY: Managers should improve relevant policies to ensure that nurses have more opportunities to participate in the practical training of health emergencies and explore effective training methods to improve the ability of nurses to respond to these.

Black phosphorus quantum dots are useful oxidase mimics for colorimetric determination of biothiols.

Black phosphorus quantum dots (BP QDs) with small size are synthesized using an easy to operate thermal method. It was found that BP QDs possess oxidase-mimicking activity. They can catalyze the oxidation of the substrate 3,3',5,5'-tetramethylbenzidine to produce a blue-colored product even in the absence of hydrogen peroxide. Active oxygen species are proved to be involved in the reaction through the experiments of radical scavenging and electron spin resonance. Biothiols including reduced glutathione and cysteine inactivate the oxidase-mimicking activity of BP QDs, concomitant to the fading of the blue solution. This provides the  base for a colorimetric method for the determination of glutathione and cysteine. The decreased absorbance at 652 nm displays linear response to the concentrations of glutathione ranging from 0.1 to 5.0 µmol L-1, and cysteine from 0.1 to 10.0 µmol L-1. The detection limits are 0.02 µmol L-1 and 0.03 µmol L-1 for glutathione and cysteine, respectively. Successive determinations of 1.0 µmol L-1 glutathione and 5.0 µmol L-1 cysteine solution give relative standard deviations of 0.8% and 1.7% (n = 11), respectively. As a preliminary application, the practicability of the method was evaluated by the determination of glutathione in pharmaceutical preparations. This work not only discovers a useful oxidase mimics but also sets up a reliable platform based on BP QDs in colorimetric detection. Graphical abstract Schematic representation of colorimetric determination for biothiols through inactivating oxidase mimetic-like catalytic activity of black phosphorus quantum dots (BP QDs) on the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with dissolved oxygen to produce its blue oxidized product (oxTMB).

Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p.

BACKGROUND: Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) are progenitor cells shown to migrate to the tumour and participate in the tumour microenvironment. BM-MSCs play important roles in tumour processes through the release of cytokines or exosomes; however, how BM-MSCs influence the stemness of CSCs in colon cancer cells remains poorly understood. METHODS: We isolated exosomes from BM-MSCs and used these exosomes to treat colon cancer cells (HCT-116, HT-29 and SW-480). We compared stemness traits of colon CSCs by cell surface marker (CD133 and Lgr5) and functional assays, such as chemoresistance, colony formation, cell adhesion, invasion and tumour-formation assay. We performed a microRNA array to investigate the differences in exosomal microRNA expression between colon cancer cells, BM-MSCs and co-cultured cells and performed functional and molecular analysis of the gene targets. RESULTS: In this study, we found that BM-MSC-derived exosomes contained distinct microRNAs, including miR-142-3p, which in turn increased the population of CSCs in colon cancer cells. Depriving miR-142-3p from BM-MSC-derived exosomes clearly decreased the population of colon CSCs. Mechanistically, Numb was found to be the target gene of miR-142-3p, and miR-142-3p promoted the Notch signalling pathway by downregulating Numb. CONCLUSIONS: Our findings indicate that BM-MSC-derived exosomes promote colon cancer stem cell-like traits via miR-142-3p.

MicroRNA-214-5p Inhibits the Invasion and Migration of Hepatocellular Carcinoma Cells by Targeting Wiskott-Aldrich Syndrome Like.

BACKGROUND/AIMS: This study aims to explore the effects of microRNA-214-5p (miR-214-5p) on the invasion and migration of Hepatocellular Carcinoma cells (HCC). METHODS: Hepatocellular Carcinoma tissues and adjacent normal tissues from 44 hepatocellular carcinoma patients were prepared for this study. The HepG2 and BEL-7402 cells were transfected with miR-214-5p mimic and inhibitor. qRT-PCR was performed to detect the expressions of miR-214-5p. Transwell assays were used to detect the invasion and migration assays in HepG2 and BEL-7402 cells. A dual-luciferase reporter assay was conducted to examine the effect of miR-214-5p on Wiskott-Aldrich Syndrome Like (WASL/ N-WASP). Western blot and qRT-PCR were used to measure the expressions of the E-cadherin, N-cadherin and Vimentin proteins. Transwell chamber assays were performed to detect cell invasion and migration. RESULTS: Compared with normal tissues, HCC tissues demonstrated significantly lower expression of miR-214-5p. Overexpression of miR-214-5p significantly inhibited the migration and invasion of HCC cells and inhibition of miR-214-5p promoted the migration and invasion. Additionally, miR-214-5p suppressed the epithelial-mesenchymal transition (EMT). Further study showed WASL was a putative target gene of miR-214-5p. Up-regulating the expression of WASL could reverse the inhibition effect of miR-214-5p on invasion and migration. CONCLUSION: Our data suggested that miR-214-5p inhibited the invasion and migration of HepG2 and BEL-7402 by targeting WASL in Hepatocellular carcinoma.

Exosomes derived from siRNA against GRP78 modified bone-marrow-derived mesenchymal stem cells suppress Sorafenib resistance in hepatocellular carcinoma.

BACKGROUND: Sorafenib is an effective clinical drug in therapy of hepatocellular carcinoma, having led to improved prognosis in hepatocellular carcinoma patients. However acquired resistance is still being encountered. So, it is urgently to develop alternative strategies to overcome drug resistance. Exosomes can be modified with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. The GRP78 is overexpressed in Sorafenib resistant cancer cells compared to Sorafenib sensitive cancer cells and thus is able to act as a target for therapy of hepatocellular carcinoma. RESULTS: In this study, we modified BM-MSCs to express the exosomal siGRP78. And we show that siGRP78 modified exosomes combined with Sorafenib is able to target GRP78 in hepatocellular carcinoma cells and inhibit the growth and invasion of the cancer cells in vitro. Further, siGRP78 modified exosomes combined with Sorafenib also inhibit the growth and metastasis of the cancer cells in vivo. CONCLUSIONS: siGRP78 modified exosomes could sensitize Sorafenib resistant cancer cells to Sorafenib and reverse the drug resistance.

The role of c-Src in the invasion and metastasis of hepatocellular carcinoma cells induced by association of cell surface GRP78 with activated α2M.

BACKGROUND: Emerging data have suggested that cell surface GRP78 is a multifunctional receptor and has been linked to proliferative and antiapoptotic signaling cascades. Activated α2-macroglobin (α2M*) is a natural circulating ligand of cell surface GRP78. Association of cell surface GRP78 with α2M* is involved in the regulation of cell proliferation, survival and apoptosis in human cancers. METHODS: The invasion and metastasis of HCC cells were examined using transwell and wound healing assay; Cell surface expression of GRP78 was detected by in cell western assay. Translocation of GRP78 from cytosol to cell surface was observed by transfection of GRP78-EGFP plus TRIRC-WGA staining. The levels of Src, phosphor-Src, FAK, phospho-FAK, EGFR, phospho-EGFR, phospho-Cortactin, phospho-Paxillin were determined by western blot. Cell surface expression of GRP78 in HCC tissue samples was observed by immunofluorescence. The distribution of Paxillin and Cortactin in HCC cells was also observed by immunofluorescence. The interaction between GRP78 and Src were detected by far-western blot, co-immunoprecipitation and GST pulldown. GRP78 mRNA was detected by RT-PCR. RESULTS: In the current study, we showed that association of cell surface GRP78 with α2M* stimulated the invasion and metastasis of HCC. Cell surface GRP78 could interact directly with c-Src, promoted the phosphorylation of c-Src at Y416. Inhibition of the tyrosine kinase activity of c-Src with PP2 reverted the stimulatory effect caused by association of cell surface GRP78 with α2M*. Moreover, association of cell surface GRP78 with α2M* facilitates the interaction between EGFR and c-Src and consequently phosphorylated EGFR at Y1101 and Y845, promoting the invasion and metastasis of HCCs. However, inhibition of the tyrosine kinase of c-Src do not affect the interaction between EGFR and Src. CONCLUSION: c-Src plays a critical role in the invasion and metastasis of HCC induced by association of cell surface GRP78 with α2M*. Cell surface GRP78 directly binds and phosphorylates c-Src. As a consequence, c-Src phosphorylated EGFR, promoting the invasion and metastasis of HCCs.

Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells.

BACKGROUND: Active targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. Various studies have demonstrated that folate and its conjugates could facilitate the chemotherapeutic drug delivery into folate receptor (FR)-positive tumor cells in vitro and in vivo. In order to utilize FA-FR binding specificity to achieve targeted delivery of drugs into tumor cells, we prepared Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-ß-cyclodextrin nanoparticles for enhancing drug delivery in cancer cells. On this context, the aim of our study was to develop a novel nano-delivery system for promoting tumor-targeting drug delivery in folate receptor-positive Hela cells. RESULTS: We prepared folic acid (FA)-decorated bovine serum albumin (BSA) conjugated carboxymethyl-ß-cyclodextrin (CM-ß-CD) nanoparticles (FA-BSA-CM-ß-CD NPs) capable of entrapping a hydrophobic Gefitinib. It was observed that nanoparticles are monodisperse and spherical nanospheres with an average diameter of 90.2 nm and negative surface charge of -18.6 mV. FA-BSA-CM-ß-CD NPs could greatly facilitate Gefitinib uptake and enhance the toxicity to folate receptor-positive Hela cells. Under the reaction between FA and FR, Gefitinib loaded FA-BSA-CM-ß-CD NPs induced apoptosis of Hela cells through elevating the expression of caspase-3 and inhibited autophagy through decreasing the expressing of LC3. It also confirmed that clathrin-mediated endocytosis and macropinocytosis exerted great influence on the internalization of both NPs. CONCLUSIONS: These results demonstrated that FA may be an effective targeting molecule and FA-BSA-CM-ß-CD NPs provided a new strategy for the treatment of human cancer cells which over-expressed folate receptors.

Cyclovirobuxine D inhibits hepatocellular carcinoma growth by inducing ferroptosis of hepatocellular carcinoma cells.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one cancer with high death rates. Nowadays, there are no effective drugs to treat it. Cyclovirobuxine D (CVB-D) is the primary ingredient of the traditional Chinese medicine (TCM) Buxus microphylla. Here, we try to explore the impacts of CVB-D on human HCC cells and explain the potential mechanisms. METHODS: HepG2 and Huh-7 cells were used for our experiments. The cell viability and half inhibitory concentration (IC50) were detected by MTT assays. The apoptosis ratio was examined by Annexin V-FITC/7AAD staining and flow cytometry (FCM). The Fe2+ content was examined by ferrous ion content assays. The malondialdehyde (MDA) content was evaluated by lipid peroxidation MDA assays. The reactive oxygen species (ROS) level was examined by the DCFH-DA probe. The expression of apoptotic markers (Bax and Bcl-2) and ferroptosis-related proteins (GPX4 and FSP1) was detected by western blotting. The in vivo curative effect of CVB was explored using xenograft models established in C-NKG mice. RESULTS: The cell viability could be inhibited by CVB-D in HepG2 and Huh-7 cells. The IC50 value of CVB-D on HepG2 and Huh-7 cells are 91.19 and 96.29 µM at 48 h, and 65.60 and 72.80 µM at 72 h. FCM showed that the apoptosis rate was increased by CVB-D in HepG2 and Huh-7 cells. Next, ferrous ion content assays showed that the level of Fe2+ was increased by CVB-D in HepG2 and Huh-7 cells. Then, we found the level of MDA and ROS was increased by CVB-D. And the Fe2+ promotion by CVB-D could be reversed by Fer-1. Additionally, western blotting assays showed that the expression of GPX4 and FSP1 was inhibited by CVB-D in HepG2 and Huh-7 cells. Moreover, in vivo, CVB-D displayed excellent anticancer effects in HCC tumor-bearing C-NKG mice. CONCLUSION: CVB-D suppresses the growth in HCC cells through ferroptosis.

Nonlinear Optimal Control Based on FBDEs and its Application to AGV.

This article focuses on solving a finite-horizon nonlinear optimal control problem by using the Pontryagin's maximum principle. In practical applications, linearization is a common approach for solving nonlinear dynamical systems. However, it is not universally applicable due to various reasons, such as instability and low accuracy. In contrast to linearization, the inherent challenge in directly solving the above nonlinear optimal control problem lies in addressing the highly coupled nonlinear forward and backward differential equations. In order to address this problem, an equivalent relationship is established between these equations and a new optimization problem. By exploiting the inherent relationship between supervised learning and an optimization problem from the view of a dynamical system, a deep neural network framework is constructed for describing the new optimization problem. Furthermore, a numerical algorithm for optimal control, which is very powerful for a large variety of nonlinear dynamical systems, is implemented by training a deep residual network. Finally, the effectiveness of the algorithm is demonstrated by solving a trajectory tracking control problem for automatic guided vehicle. The obtained results reveal that the proposed control scheme can achieve high-precision tracking.

Tumor targeted cancer membrane-camouflaged ultra-small Fe nanoparticles for enhanced collaborative apoptosis and ferroptosis in glioma.

Glioma is recognized as the most common and aggressive primary brain tumor in adults. Owing to the occurrence of drug resistance and the failure of drug to penetrate the blood-brain barrier (BBB), there is no effective strategy for the treatment of glioma. The main objective of this study was to develop a biomimetic glioma C6 cell membrane (C6M) derived nanovesicles (DOX-FN/C6M-NVs) loaded with doxorubicin (DOX) and ultra-small Fe nanoparticles (FN) for accomplishing the effective brain tumor-targeted delivery of DOX and improving anti-cancer efficacy via inducing collaborative apoptosis and ferroptosis. The findings revealed that employing C6M-NVs as a carrier significantly improved the therapeutic efficacy by enabling evasion of immune surveillance, facilitating targeted drug delivery to tumor sites, and minimizing cardiotoxicity and adverse effects associated with DOX. DOX-FN/C6M-NVs exhibited more potent anti-tumor effects as compared with free DOX by promoting DOX-mediated apoptosis and accelerating ferroptosis via the mediation of FN. This study suggested that DOX-FN/C6M-NVs as the potential inducer of ferroptosis and apoptosis conferred effective tumor suppression in the treatment of glioma.

Real-time dense small object detection algorithm based on multi-modal tea shoots.

Introduction: The difficulties in tea shoot recognition are that the recognition is affected by lighting conditions, it is challenging to segment images with similar backgrounds to the shoot color, and the occlusion and overlap between leaves. Methods: To solve the problem of low accuracy of dense small object detection of tea shoots, this paper proposes a real-time dense small object detection algorithm based on multimodal optimization. First, RGB, depth, and infrared images are collected form a multimodal image set, and a complete shoot object labeling is performed. Then, the YOLOv5 model is improved and applied to dense and tiny tea shoot detection. Secondly, based on the improved YOLOv5 model, this paper designs two data layer-based multimodal image fusion methods and a feature layerbased multimodal image fusion method; meanwhile, a cross-modal fusion module (FFA) based on frequency domain and attention mechanisms is designed for the feature layer fusion method to adaptively align and focus critical regions in intra- and inter-modal channel and frequency domain dimensions. Finally, an objective-based scale matching method is developed to further improve the detection performance of small dense objects in natural environments with the assistance of transfer learning techniques. Results and discussion: The experimental results indicate that the improved YOLOv5 model increases the mAP50 value by 1.7% compared to the benchmark model with fewer parameters and less computational effort. Compared with the single modality, the multimodal image fusion method increases the mAP50 value in all cases, with the method introducing the FFA module obtaining the highest mAP50 value of 0.827. After the pre-training strategy is used after scale matching, the mAP values can be improved by 1% and 1.4% on the two datasets. The research idea of multimodal optimization in this paper can provide a basis and technical support for dense small object detection.

Exosomes from bone marrow mesenchymal stem cells are a potential treatment for ischemic stroke.

Exosomes derived from human bone marrow mesenchymal stem cells (MSC-Exo) are characterized by easy expansion and storage, low risk of tumor formation, low immunogenicity, and anti-inflammatory effects. The therapeutic effects of MSC-Exo on ischemic stroke have been widely explored. However, the underlying mechanism remains unclear. In this study, we established a mouse model of ischemic brain injury induced by occlusion of the middle cerebral artery using the thread bolt method and injected MSC-Exo into the tail vein. We found that administration of MSC-Exo reduced the volume of cerebral infarction in the ischemic brain injury mouse model, increased the levels of interleukin-33 (IL-33) and suppression of tumorigenicity 2 receptor (ST2) in the penumbra of cerebral infarction, and improved neurological function. In vitro results showed that astrocyte-conditioned medium of cells deprived of both oxygen and glucose, to simulate ischemia conditions, combined with MSC-Exo increased the survival rate of primary cortical neurons. However, after transfection by IL-33 siRNA or ST2 siRNA, the survival rate of primary cortical neurons was markedly decreased. These results indicated that MSC-Exo inhibited neuronal death induced by oxygen and glucose deprivation through the IL-33/ST2 signaling pathway in astrocytes. These findings suggest that MSC-Exo may reduce ischemia-induced brain injury through regulating the IL-33/ST2 signaling pathway. Therefore, MSC-Exo may be a potential therapeutic method for ischemic stroke.

Body mass index and outcomes of patients with cardiogenic shock: A systematic review and meta-analysis.

BACKGROUND: Cardiogenic shock continues to be a highly morbid complication that affects around 7%-10% of patients with acute myocardial infarction or heart failure. Similarly, obesity has become a worldwide epidemic. AIM: To analyze the impact of higher body mass index (BMI) on outcomes of patients with cardiogenic shock. METHODS: A systematic and comprehensive search was undertaken on the electronic databases of PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar for all types of studies comparing mortality outcomes of patients with cardiogenic shock based on BMI. All studies defined overweight or obese patients based on the World Health Organization BMI criteria. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS: Five studies were included. On pooled analysis of multivariable-adjusted ratios, we noted a statistically significantly reduced risk of mortality in overweight/obese vs normal patients (three studies; odds ratio [OR] = 0.92, 95% confidence interval [CI]: 0.85-0.98, I 2 = 85%). On meta-analysis, we noted that crude mortality rates did not significantly differ between overweight/obese and normal patients after cardiogenic shock (OR = 0.95, 95%CI: 0.79-1.15, I 2 = 99%). The results were not stable on sensitivity analysis and were associated with substantial heterogeneity. CONCLUSION: Current evidence on the association between overweight/obesity and mortality after cardiogenic shock is scarce and conflicting. The obesity paradox might exist in patients with cardiogenic shock but could be confounded by the use of mechanical circulatory support. There is a need for further studies to clarify this relationship.

A multifunctional antibacterial and self-healing hydrogel laden with bone marrow mesenchymal stem cell-derived exosomes for accelerating diabetic wound healing.

Chronic diabetic wound injury is a serious syndrome of diabetes, and the treatment of this syndrome is of great significance. Owing to metabolic abnormalities, diabetic wounds are difficult to heal due to chronic inflammation, immune dysfunction, impaired angiogenesis and bacterial reproduction. However, most traditional treatments can only play a limited role in dealing with unhealed wounds, and the overall healing effect is not ideal. We designed a novel bone marrow mesenchymal stem cell-derived exosome (MSC-Exo)-loaded carboxyethyl chitosan (CEC)-dialdehyde carboxymethyl cellulose (DCMC) hydrogel (MSC-Exos@CEC-DCMC HG) for chronic diabetic wound healing. The results demonstrated that CEC can be cross-linked with DCMC through Schiff base reactions to form antibacterial and self-healing hydrogels. The inherent MSC-Exos not only promoted angiogenesis but also enhanced the transformation of M1-type macrophages to the M2 type to reduce inflammatory effects. Finally, MSC-Exos@CEC-DCMC HG, as an effective therapeutic agent, synergistically adjusted the wound inflammation microenvironment, promoted neovascularization, and accelerated wound healing in type 1 diabetic rats.

A novel luminol chemiluminescence system induced by black phosphorus quantum dots for cobalt (II) detection.

Black phosphorus quantum dots (BP QDs) were prepared through a solvothermal exfoliation method in alkaline N-methyl-2-pyrrolidinone. The BP QDs induce distinct chemiluminescence (CL) of alkaline luminol directly. A possible reaction mechanism is proposed by the study of CL spectrum, ultraviolet-visible absorption spectra, electron paramagnetic resonance spectra as well as radical scavenging experiments. The presence of BP QDs significantly increases generation of active oxygen species, which oxidize luminol and lead to intense CL emission at 425 nm. The reaction of luminol with BP QDs are specifically catalyzed by cobalt (II) ion, this presents a sensitive CL method for cobalt (II) ion. A linear response range extends from 2.5 to 2000.0 pmol/L cobalt (II) ion and a detection limit of 0.7 pmol/L (3sb) is acquired. The method displays a good precision approved by a relative standard deviation of 1.9% at 100.0 pmol/L cobalt (II) ion solution (n = 11). A preliminary application of the method was conducted by successful determination of cobalt amount in silica gel and rain water samples.

Grp78 promotes the invasion of hepatocellular carcinoma.

BACKGROUND: Glucose regulated protein 78 (Grp78) is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism. METHODS: The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+)-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining. RESULTS: Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased RhoA-GTP level, and Grp78 siRNA knockdown rescued RhoA-GTP level in Grp78 overexpressing cells, indicating Grp78 inhibited RhoA activity in hepatocellular carcinoma cells. Furthermore, overexpression of Grp78 in SMMC7721 cells increased phospho-p190RhoGAP level. FAK siRNA knockdown in Grp78 overexpressing cells reversed phospho-p190RhoGAP level. These data suggested that Grp78 inhibited RhoA activity by up-regulated phospho-p190RhoGAP level and Grp78 mediated p190RhoGAP phosphorylation is FAK dependent. CONCLUSION: Grp78 promoted the invasion of hepatocellular carcinoma both in vitro and in vivo. Overexpression of Grp78 in hepatocellular carcinoma cells enhanced the activation and activity of FAK which negatively regulated Rock kinase activity by promoting the phosphorylation of p190RhoGAP.

Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition.

Lung cancer is the leading cause of cancer-related deaths worldwide. Tumor suppressor genes remain to be systemically identified for lung cancer. Through the genome-wide screening of tumor-suppressive transcription factors, we demonstrate here that GATA4 functions as an essential tumor suppressor in lung cancer in vitro and in vivo. Ectopic GATA4 expression results in lung cancer cell senescence. Mechanistically, GATA4 upregulates multiple miRNAs targeting TGFB2 mRNA and causes ensuing WNT7B downregulation and eventually triggers cell senescence. Decreased GATA4 level in clinical specimens negatively correlates with WNT7B or TGF-ß2 level and is significantly associated with poor prognosis. TGFBR1 inhibitors show synergy with existing therapeutics in treating GATA4-deficient lung cancers in genetically engineered mouse model as well as patient-derived xenograft (PDX) mouse models. Collectively, our work demonstrates that GATA4 functions as a tumor suppressor in lung cancer and targeting the TGF-ß signaling provides a potential way for the treatment of GATA4-deficient lung cancer.