A spatiotemporal barrier formed by Follistatin is required for left-right patterning.

How left-right (LR) asymmetry emerges in a patterning field along the anterior-posterior axis remains an unresolved problem in developmental biology. Left-biased Nodal emanating from the LR organizer propagates from posterior to anterior (PA) and establishes the LR pattern of the whole embryo. However, little is known about the regulatory mechanism of the PA spread of Nodal and its asymmetric activation in the forebrain. Here, we identify bilaterally expressed Follistatin (Fst) as a regulator blocking the propagation of the zebrafish Nodal ortholog Southpaw (Spaw) in the right lateral plate mesoderm (LPM), and restricting Spaw transmission in the left LPM to facilitate the establishment of a robust LR asymmetric Nodal patterning. In addition, Fst inhibits the Activin-Nodal signaling pathway in the forebrain thus preventing Nodal activation prior to the arrival, at a later time, of Spaw emanating from the left LPM. This contributes to the orderly propagation of asymmetric Nodal activation along the PA axis. The LR regulation function of Fst is further confirmed in chick and frog embryos. Overall, our results suggest that a robust LR patterning emerges by counteracting a Fst barrier formed along the PA axis.

Clear Cell Renal Cell Carcinoma: Characterizing the Phenotype of Von Hippel-Lindau Mutation Using MRI.

BACKGROUND: The von Hippel-Lindau (VHL) mutation is an important alteration in clear cell renal cell carcinoma (ccRCC); however, its imaging phenotype remains unclear. PURPOSE: To investigate whether MRI features can reflect the VHL mutation status. STUDY TYPE: Retrospective. FIELD STRENGTH/SEQUENCE: 3 T/fast spin echo T2-weighted, spin-echo echo planar diffusion-weighted, gradient recalled echo T1-weighted, gradient recalled echo chemical-shift T1-weighted, and contrast-enhanced gradient recalled echo T1-weighted sequences. POPULATION: One hundred five patients with ccRCC who underwent preoperative contrast-enhanced MRI and subsequent genomic sequencing: 59 consecutive patients from our institution (38 [64.41%] with VHL mutations) formed a training cohort, and 46 from The Cancer Genome Atlas (TCGA) database (24 [52.17%] with VHL mutations) formed an independent test cohort. ASSESSMENT: Two radiologists, with 23 and 33 years of experience respectively, jointly evaluated the semantic MRI features of the primary lesion in ccRCCs to propose potential features related to VHL mutations in both cohorts. Three additional readers, with 5, 7, and 10 years of experience respectively, independently reviewed all lesions to assess the interobserver agreement of MRI features. A VHL mutational likelihood score (VHL-MULIS) system was constructed using the training cohort and validated using the independent test cohort. STATISTICAL TESTS: Fisher's test or chi-square test, t-test or Mann-Whitney U test, logistic regression, Cohen's kappa (κ), area under the receiver operating characteristic curve (AUC). A two-sided P value <0.05 was considered statistically significant. RESULTS: In both the local and public cohorts, T2-weighted signal intensity and presence of microscopic fat from primary lesions were significantly associated with VHL mutation status. The VHL-MULIS incorporated maximum diameter, T2-weighted signal intensity, and presence of microscopic fat in the training cohort and demonstrated promising diagnostic ability (AUC, 0.82; sensitivity, 0.79; specificity, 0.82) and substantial interobserver agreement (κ, 0.787) in the test cohort. DATA CONCLUSION: The VHL mutation exhibited a distinct MRI phenotype. Integrating multiple semantic MRI features has potential to reflect the mutation status in patients with ccRCC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Fluid absorption during flexible ureteroscopy with intelligent control of renal pelvic pressure: a randomized controlled trial.

PURPOSE: To investigate fluid absorption and its influencing factors during flexible ureteroscopy with intelligent control of renal pelvic pressure (RPP). METHODS: A total of 80 patients with upper urinary tract calculi underwent flexible ureteroscopy with intelligent control of RPP by pressure-measuring ureteral access sheath and were randomly divided into four groups. The RPP of Groups A, B, and C were set at - 5, 0 and 5 mmHg, respectively. Conventional flexible ureteroscopy with uncontrolled pressure served as control Group D. The perfusion flow rate was set at 100 ml/min in the four groups, with 20 patients in each group. The fluid absorption was measured by 1% ethanol every 10 min. Operation time, stone-free rate, and complications were recorded. RESULT: Seventy-three patients were finally included in the RCT. The general and preoperative data of the patients were comparable between the groups. The fluid absorption of Groups A, B, and C was significantly less than that of Group D (P < 0.01). Fluid absorption and operation time were positively correlated, and the correlation coefficients R were 0.864, 0.896, 0.918, and 0.947, respectively (P < 0.01). The fluid absorption of patients with vomiting, fever and ureteral injury was greater than that of patients without complications in the four groups (P < 0.01). In different groups, fluid absorption was greater in patients with ureteral injury Post-Ureteroscopic Lesion Scale (PULS) 1-3 than in noninjured patients (P < 0.01). CONCLUSION: Flexible ureteroscopy with intelligent control of RPP effectively reduces the absorption of perfusion fluid. Operation time and ureteral injury are also key factors affecting perfusion fluid absorption. REGISTRATION NUMBER AND DATE: NCT05201599; August 11, 2021.

Expression of a thermostable glucose-stimulated ß-glucosidase from a hot-spring metagenome and its promising application to produce gardenia blue.

This study reports a thermostable glucose-stimulated ß-glucosidase, BglY442, from hot-spring metagenomic data that was cloned and expressed in Escherichia coli BL21 (DE3). The molecular mass of recombinant BglY442 was 69.9 kDa and was used in the production of gardenia blue. The recombinant BglY442 showed its maximum activity at pH 6.0 and 75 °C, maintained 50 % activity at 70 °C for 36 h, presented over 90 % activity in a broad pH range and a wide range of pH stability. Moreover, BglY442 exhibited excellent tolerance toward methanol and ethanol. The specific activity of BglY442 was 235 U/mg at pH 6.0 and 75 °C with 10 mM pNPG as substrate. BglY442 activity increased by over fourfold with 2 M glucose or xylose. Specifically, the enzyme kinetics of BglY442 seem to be non-Michaelis-Menten kinetics or atypical kinetics because the Michaelis-Menten saturation kinetics were not observed with pNPG, oNPG or geniposide as substrates. Under optimum conditions, geniposide was dehydrated by BglY442 and reacted with nine amino acids respectively by the one-pot method. Only the Arg or Met derived pigments showed bright blue, and these two pigments had similar ultraviolet absorption spectra. The OD590 nm of GB was detected to be 1.06 after 24 h with the addition of Arg and 1.61 after 36 h with the addition of Met. The intermediate was elucidated and identified as ginipin. Molecular docking analysis indicated that the enzyme had a similar catalytic mechanism to the reported GH1 Bgls. BglY442 exhibited potential for gardenia blue production by the one-pot method. With outstanding thermostability and glucose tolerance, BglY442 should be considered a potential ß-glucosidase in biotechnology applications.

Flexible Ureteroscopy with a Tip-Flexible Pressure-Controlling Ureteral Access Sheath for Renal Stones in Children.

INTRODUCTION: The aim of this study was to evaluate the safety and efficacy of flexible ureteroscopy using a tip-flexible pressure-controlling ureteral access sheath (TFPC-UAS) for renal stones in children. METHODS: Consecutive patients aged 5-18 years with renal stones of diameter 1-3 cm were enrolled between January 2022 and November 2023 at Ganzhou People's Hospital. The patients were treated with flexible ureteroscopy using the TFPC-UAS. The renal pelvic pressure (RPP) parameters were set as follows: control value at -10 mm Hg to 5 mm Hg, warning value at 20 mm Hg, and limit value at 30 mm Hg. The infusion flow rate was set to 100-120 mL/min. A holmium laser (276 µm) was used to fragment the stone at 2.0-2.5 J/pulse with a frequency of 20-30 pulses/s. The cases were analyzed for RPP, operative time, stone-free rate, and complications. RESULTS: A total of 21 consecutive patients were included. Two patients were switched to percutaneous nephrolithotomy owing to sheath placement failure. The RPP was -4.6 ± 2.1 mm Hg. The mean operative time was 56.5 ± 17.1 min. The postoperative hospitalization time was 1.5 ± 0.3 days. The stone-free rates at 1 day and 1 month after surgery were 81.0% and 85.7%, respectively. Residual stones in 2 patients were cleared after extracorporeal shockwave lithotripsy. Three cases of Clavien I complications and one case of Clavien II complications occurred. No major complications (Clavien grade III-V) were observed. CONCLUSIONS: Flexible ureteroscopy with a TFPC-UAS is safe and effective for renal stones in children.

Physicians' knowledge of invasive fungal disease in China.

BACKGROUND: Invasive fungal disease (IFD) is associated with high morbidity and mortality. Data are lacking regarding physicians' perspectives on the diagnosis and management of IFD in China. OBJECTIVES: To evaluate physicians' perspectives on the diagnosis and management of IFD. METHODS: Based on current guidelines, a questionnaire was designed and administered to 294 physicians working in haematology departments, intensive care units, respiratory departments and infectious diseases departments in 18 hospitals in China. RESULTS: The total score and subsection scores for invasive candidiasis, invasive aspergillosis (IA), cryptococcosis and invasive mucormycosis (IM) were 72.0 ± 12.2 (maximum = 100), 11.1 ± 2.7 (maximum = 19), 43.0 ± 7.8 (maximum = 57), 8.1 ± 2.0 (maximum = 11) and 9.8 ± 2.3 (maximum = 13), respectively. Although the perspectives of the Chinese physicians were in good overall agreement with guideline recommendations, some knowledge gaps were identified. Specific areas in which the physicians' perspectives and guideline recommendations differed included use of the ß-D-glucan test to facilitate the diagnosis of IFD, relative utility of the serum galactomannan test and bronchoalveolar lavage fluid galactomannan test in patients with agranulocytosis, use of imaging in the diagnosis of mucormycosis, risk factors for mucormycosis, indications for initiating antifungal therapy in patients with haematological malignancies, when to start empirical therapy in mechanically ventilated patients, first-line drugs for mucormycosis and treatment courses for IA and IM. CONCLUSION: This study highlights the main areas that could be targeted by training programs to improve the knowledge of physicians treating patients with IFD in China.

Ticlopidine induces embryonic development toxicity and hepatotoxicity in zebrafish by upregulating the oxidative stress signaling pathway.

Ticlopidine exerts its anti-platelet effects mainly by antagonizing platelet p2y12 receptors. Previously, a few studies have shown that ticlopidine can induce liver injury, but the exact mechanism of hepatotoxicity remains unclear. Oxidative stress, metabolic disorders, hepatocyte apoptosis, lipid peroxidation, and inflammatory responses can all lead to hepatic liver damage, which can cause hepatotoxicity. In this study, in order to deeply explore the potential molecular mechanisms of ticlopidine -induced hepatotoxicity, we used zebrafish as a model organism to comprehensively evaluate the hepatotoxicity of ticlopidine and its associated mechanism. Three days post-fertilization, zebrafish larvae were exposed to varying concentrations (1.5, 1.75 and 2 µg/mL) of ticlopidine for 72 h, in contrast, adult zebrafish were exposed exposure to 4 µg/mL of ticlopidine for 28 days. Ticlopidine-exposed zebrafish larvae showed changes in liver morphology, shortened body length, and delayed development of the swim bladder development. Liver tissues of ticlopidine-exposed zebrafish larvae and adults stained with Hematoxylin & Eosin revealed vacuolization and increased cellular interstitial spaces in liver tissues. Furthermore, using Oil Red O and periodic acid-Schiff staining methods and evaluating different metabolic enzymes of ticlopidine-exposed zebrafish larvae and adults suggested abnormal liver metabolism and liver injury in both ticlopidine-exposed zebrafish larvae and adults. Ticlopidine also significantly elevated inflammation and oxidative stress and reduced hepatocyte proliferation. During the rescue intervention using N-acetylcysteine, we observed significant improvement in ticlopidine-induced morphological changes in the liver, shortened body length, delayed swim bladder development, and proliferation of liver tissues showed significant improvement. In conclusion, ticlopidine might inhibit normal development and liver proliferation in zebrafish by upregulation of oxidative stress levels, thus leading to embryonic developmental toxicity and hepatotoxicity. In this study, we used zebrafish as a model organism to elucidate the developmental toxicity and hepatotoxicity induced by ticlopidine upregulation of oxidative stress signaling pathway in zebrafish, providing a theoretical basis for clinical application.

Transcription and proteome changes involved in re-innervation muscle following nerve crush in rats.

Severe peripheral nerve injury leads to the irreparable disruption of nerve fibers. This leads to disruption of synapses with the designated muscle, which consequently go through progressive atrophy and damage of muscle function. The molecular mechanism that underlies the re-innervation process has yet to be evaluated using proteomics or transcriptomics. In the present study, multi-dimensional data were therefore integrated with transcriptome and proteome profiles in order to investigate the mechanism of re-innervation in muscles. Two simulated nerve injury muscle models in the rat tibial nerve were compared: the nerve was either cut (denervated, DN group) or crushed but with the nerve sheath intact (re-innervated, RN group). The control group had a preserved and intact tibial nerve. At 4 weeks, the RN group showed better tibial nerve function and recovery of muscle atrophy compared to the DN group. As the high expression of Myh3, Postn, Col6a1 and Cfi, the RN group demonstrated superior re-innervation as well. Both differentially expressed genes (DEGs) and proteins (DEPs) were enriched in the peroxisome proliferator-activated receptors (PPARs) signaling pathway, as well as the energy metabolism. This study provides basic information regarding DEGs and DEPs during re-innervation-induced muscle atrophy. Furthermore, the crucial genes and proteins can be detected as possible treatment targets in the future.

Quantum Interference-Controlled Conductance Enhancement in Stacked Graphene-like Dimers.

Stacking interactions are of significant importance in the fields of chemistry, biology, and material optoelectronics because they determine the efficiency of charge transfer between molecules and their quantum states. Previous studies have proven that when two monomers are π-stacked in series to form a dimer, the electrical conductance of the dimer is significantly lower than that of the monomer. Here, we present a strong opposite case that when two anthanthrene monomers are π-stacked to form a dimer in a scanning tunneling microscopic break junction, the conductance increases by as much as 25 in comparison with a monomer, which originates from a room-temperature quantum interference. Remarkably, both theory and experiment consistently reveal that this effect can be reversed by changing the connectivity of external electrodes to the monomer core. These results demonstrate that synthetic control of connectivity to molecular cores can be combined with stacking interactions between their π systems to modify and optimize charge transfer between molecules, opening up a wide variety of potential applications ranging from organic optoelectronics and photovoltaics to nanoelectronics and single-molecule electronics.

Single-molecule nano-optoelectronics: insights from physics.

Single-molecule optoelectronic devices promise a potential solution for miniaturization and functionalization of silicon-based microelectronic circuits in the future. For decades of its fast development, this field has made significant progress in the synthesis of optoelectronic materials, the fabrication of single-molecule devices and the realization of optoelectronic functions. On the other hand, single-molecule optoelectronic devices offer a reliable platform to investigate the intrinsic physical phenomena and regulation rules of matters at the single-molecule level. To further realize and regulate the optoelectronic functions toward practical applications, it is necessary to clarify the intrinsic physical mechanisms of single-molecule optoelectronic nanodevices. Here, we provide a timely review to survey the physical phenomena and laws involved in single-molecule optoelectronic materials and devices, including charge effects, spin effects, exciton effects, vibronic effects, structural and orbital effects. In particular, we will systematically summarize the basics of molecular optoelectronic materials, and the physical effects and manipulations of single-molecule optoelectronic nanodevices. In addition, fundamentals of single-molecule electronics, which are basic of single-molecule optoelectronics, can also be found in this review. At last, we tend to focus the discussion on the opportunities and challenges arising in the field of single-molecule optoelectronics, and propose further potential breakthroughs.

Evaluating the effect of anti-nausea drugs in IDO enzyme gene expression and preventing postoperative vomiting and nausea in patients undergoing general anesthesia: A Meta-analysis.

Nausea and vomiting are known as side effects after surgery. Since serotonin antagonist drugs are widely used to prevent nausea and vomiting after surgery, the present study was conducted to compare the effectiveness of this group's drugs, namely, ondansetron and palonosetron. On the other hand, recent studies have shown that the metabolites of the kynurenine pathway in the Suppression of the immune response play a role. Indoleamine 2,3 dioxygenase (IDO) is the main enzyme controlling this pathway. Therefore, the effect of these two drugs on IDO gene expression was evaluated. The present study is a systematic review with meta-analysis. The search was conducted in the Cochrane, PubMed, Clinical K, and CRD databases for randomized clinical trial articles that compared two drugs, palonosetron, and ondansetron, regarding nausea and vomiting in patients undergoing surgery with general anesthesia. In the end, eight studies were included in the meta-analysis. STATA13 statistical software was used to estimate the overall risk, relative risk, and data analysis. The results showed that the number of samples in all articles was 739. The analysis of the results between 0 and 24 hours showed that palonosetron reduces the incidence of nausea by 50% and the incidence of vomiting by 79% compared to ondansetron (p=0.001). Also, there was no difference between the IDO gene expression in the two drug groups (p>0.05). In general, the analysis of the results related to the effectiveness of palonosetron and ondansetron 24 hours after surgery with a dose of 0.075 mg of palonosetron versus 4 mg of ondansetron showed that palonosetron is more effective in reducing the incidence of nausea and vomiting in patients than ondansetron.

A systematic review on considering the role of Magnesium in preventing post-anesthesia shivering.

Shivering following anesthesia is caused by disturbed regulation of body temperature and causes an increase in tissue oxygen consumption and cardio-pulmonary activity. Choosing the right medicine to reduce shivering with the most negligible side effects in surgery is essential. Magnesium is prescribed intravenously, epidurally, or intra-peritoneally. Each of these methods can have different effects in different surgical operations. In this review, we are looking for randomized clinical trials that compared preoperative magnesium administration with a control group and included studies that evaluated the degree of shivering as a primary outcome variable. This study aimed to evaluate pre-operative magnesium's effect in preventing shivering after surgery. This article was a systematic review type, in which all quality articles published until the end of 2021 were searched with the keywords magnesium, shivering, surgery, and prevention via different databases, including PubMed, Cochrane Central Register of Tested Controlled, EMBASE and Web of Science. In the initial search, 3294 publications were identified. 64 articles were included in this study. The results indicated that shivering in the magnesium group with IV epidural injection inside the peritoneum was significantly reduced compared to the control group. It was also identified in the examination of symptoms. Variants such as extubation time, length of stay in PACU, magnesium serum concentration, spinal c-fos mRNA expression, nausea or vomiting, sedation, itching, pressure drop, and bradycardia were significantly less reported than the control group. In general, the results showed that the preventive use of magnesium could decrease the intensity and number of post-anesthesia shivering and other post-anesthesia symptoms.

Early Renal-Replacement Therapy May Reduce the All-Cause Mortality of Severe COVID-19: An Observational Cohort Study.

INTRODUCTION: The efficacy of renal-replacement treatment (RRT) remains to be validated in COVID-19. In this retrospective cohort study, we aimed to assess the efficacy of early initiation of RRT in intensive care unit (ICU) adults with severe COVID-19. METHODS: Fifty-eight adult patients in ICU with critically ill or severe COVID-19 with a tendency of critical illness were recruited from February 9, 2020, to March 30, 2020. Early RRT were determined by the ICU medical team based on boom in cytokines levels, increased organs injury/failure, and rapid aggravation of condition. All participants were followed up from the first day of ICU admission to March 30, 2020. The primary outcome was all-cause mortality in ICU. RESULTS: The mean age of the cohort was 68.4 ± 14.6 years, with 81.0% having at least one comorbidity before hospitalization. Twenty patients (34.5%) initiated early RRT after 24.1 ± 10.4 days from the onset and 6.4 ± 3.6 days from ICU admission. Thirty-four of 58 participants (58.6%) died during ICU follow-up. Univariate and multivariate Cox proportional-hazards model showed that early RRT was associated with a lower risk of all-cause mortality in ICU with an adjusted HR of 0.280 (95% CI: 0.106-0.738, p = 0.010). Sudden unexpected death (SUD) was remarkably reduced in the early RRT group, compared with the control group (0.2 vs. 2.9 per 100 person-day, p = 0.02). CONCLUSION: Early RRT can reduce the all-cause in-hospital mortality, especially SUD in patients with severe COVID-19, but not improve multi-organ impairment or increase the risk of AKI. Early initiation of RRT merits an optional strategy in critically ill patients with COVID-19 (ChiCTR2000030773).

Ticlopidine induces cardiotoxicity in zebrafish embryos through AHR-mediated oxidative stress signaling pathway.

Ticlopidine has inhibitory effects on platelet aggregation via ADP (adenosine diphosphate), platelet release reaction and depolymerization. In clinical practice, it is commonly used to prevent heart, cerebrovascular and other thromboembolic diseases. However, ticlopidine has also been reported to have teratogenic effects on the heart, though its specific molecular mechanism remains unclear. In this study, zebrafish embryos were used as model organisms to examine the toxicity effect of ticlopidine. Zebrafish embryos exposed to 6, 7.5, and 9 mg/L ticlopidine solutions manifested several abnormalities, including body curvature, smaller eyes, slower absorption of the vitella sac, pericardial edema, slower heart rate, increased mortality, longer venous sinus - arterial ball (SV-BA) distance, and increased oxidative stress, which indicated developmental and cardiac toxicity. Abnormal expression of key genes related to heart development was observed, and the level of apoptotic gene expression was up-regulated. Further experiments revealed up-regulation of embryonic oxidative stress following ticlopidine exposure, leading to a decrease in cardiomyocyte proliferation. Conversely, the aromatic hydrocarbon receptor (AHR) inhibitor CH223191 protected embryos from the cardiotoxicity effect of ticlopidine, confirming further the role of up-regulated oxidative stress as the molecular mechanism of ticlopidine-induced cardiotoxicity in zebrafish. In conclusion, ticlopidine exposure leads to developmental and cardiotoxicity in zebrafish embryos. Therefore, further studies are warranted to ascertain such potential harms of ticlopidine in humans, which are vital in providing guidance in the safe use of drugs in clinical practice.

Combining reverse end-to-side neurorrhaphy with rapamycin treatment on chronically denervated muscle in rats.

This preliminary research determines whether a combination of reverse end-to-side neurorrhaphy and rapamycin treatment achieves a better functional outcome than a single application after prolonged peripheral nerve injury. We found that the tibial nerve function of the reverse end-to-side + rapamycin group recovered better, with a higher tibial function index value, higher amplitude recovery rate, and shorter latency delay rate (P < 0.05). The reverse end-to-side + rapamycin group better protected the gastrocnemius muscle with more forceful contractility, tetanic tension, and a higher myofibril cross-sectional area (P < 0.05). Combining reverse end-to-side neurorrhaphy with rapamycin treatment is a practical approach to promoting the recovery of chronically denervated muscle atrophy after peripheral nerve injury.

Fine mapping of restorer-of-fertility gene based on high-density genetic mapping and collinearity analysis in pepper (Capsicum annuum L.).

KEY MESSAGE: The pepper restorer-of-fertility (CaRf) gene was fine mapped based on conjoint analysis of recombinants and collinearity between the two pepper reference genomes. Capana06g003028, encoding an Rf-like PPR protein, was proposed as the strongest candidate for pepper CaRf based on sequence comparison and expression analysis. The cytoplasmic male sterility (CMS)/restorer-of-fertility (Rf) system not only provides an excellent model to dissect genetic interactions between the mitochondria and nucleus but also plays a vital role in high-efficiency hybrid seed production in crops including pepper (Capsicum spp.). Although two important CMS candidate genes, orf507 and Ψatp6-2, have previously been suggested, the pepper Rf gene (CaRf) has not yet been isolated. In this study, a high-density genetic map comprising 7566 SNP markers in 1944 bins was first constructed with the array genotyping results from 317 F2 individuals. Based on this map, the CaRf gene was preliminarily mapped to a region of 1.15 Mb in length at the end of chromosome P6. Then, by means of a conjoint analysis of recombinants and collinearity between the two pepper reference genomes, an important candidate interval with 270.10 kb in length was delimited for CaRf. Finally, Capana06g003028, which encodes an Rf-like PPR protein, was proposed as the strongest candidate for CaRf based on sequence analysis and expression characteristics in sterile and fertile plants. The high-density genetic map and fine mapping results provided here lay a foundation for the application of molecular breeding, as well as cloning and functional analysis of CaRf, in pepper.

Secure Drone Network Edge Service Architecture Guaranteed by DAG-Based Blockchain for Flying Automation under 5G.

With the development of the Internet of Things (IoT), the number of drones, as a consumer-level IoT device, is rapidly increasing. The existence of a large number of drones increases the risk of misoperation during manual control. Therefore, it has become an inevitable trend to realize drone flying automation. Drone flying automation mainly relies on massive drone applications and services as well as third-party service providers, which not only complicate the drone network service environment but also raise some security and privacy issues. To address these challenges, this article proposes an innovative architecture called Secure Drone Network Edge Service (SDNES), which integrates edge computing and blockchain into the drone network to provide real-time and reliable network services for drones. To design a feasible and rational SDNES architecture, we first consider the real-time performance and apply edge computing technology in it to provide low-latency edge services for drones under 5G mobile network. We use DAG-based blockchain to guarantee the security and reliability of the drone network service environment and effectively avoid malicious behaviors. In order to illustrate the feasibility of this architecture, we design and implement a specific service case named Drone Collision Avoidance Navigation Service based on SDNES. Finally, a simulation experiment for the specific service case and a series of other performance-related experiments were carried out to verify the feasibility and rationality of our proposed architecture. The experimental results demonstrate that SDNES is a promising architecture to assist and accelerate drone flying automation.

[A new phenolic compound from endophytic fungus Aspergillus fumigatus of Euphorbia royleana].

This research was carried out to study the secondary metabolites of endophytic fungus Aspergillosis fumigatus from Euphorbia royleana. The endophytic fungus A. fumigatus was fermented by solid fermentation,and purified by various chromatographic methods after extraction. The structures of the compounds were identified by1 H-NMR,13 C-NMR and HSQC,HMBC spectra and physicchemical properties. Three compounds were isolated and their structures were identified as 3-( 3,4-dihydroxybenzoyl)-5-( 3,4-dihydroxyphenyl)-6-methyl-5,6-dihydro-2 H-pyran-2-one( 1),hydroxysydonic acid( 2) and 11-hydroxysydonic acid( 3). Compound 1 is a new compound.

Adiponectin Inhibits TNF-α-Activated PAI-1 Expression Via the cAMP-PKA-AMPK-NF-κB Axis in Human Umbilical Vein Endothelial Cells.

BACKGROUND: Tumor necrosis factor (TNF)-α can upregulate the expression of plasminogen activator inhibitor (PAI)-1, an inhibitor of fibrinolysis. Adiponectin (Adp) antagonizes TNF-α by negatively regulating its expression in various tissues. In the present study, the ability of Adp to suppress TNF-α-induced PAI-1 upregulation and the underlying mechanisms were evaluated. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with TNF-α in the presence or absence of Adp, and PAI-1 mRNA and antigen expression, activated signaling pathways, and molecular mechanisms were analyzed by qRT-PCR and ELISA. RESULTS: Adp decreased the TNF-α-induced upregulation of PAI-1 mRNA and protein expression and suppressed TNF-α-induced cAMP-PKA-AMPK inactivation. Adp also suppressed the TNF-α-induced NF-kB binding capability on the PAI-1 promoter. Moreover, these Adp-induced effects were further enhanced or prevented by treatment with the cAMP inhibitor Rp-cAMPs or activator forskolin, respectively. CONCLUSIONS: Our data suggest that Adp abrogates TNF-α-activated PAI-1 expression by activating cAMP-PKA-AMPK signaling to suppress NF-kB binding to the PAI-1 promoter in HUVECs. Given the antifibrotic effect of PAI-1 abrogation, Adp may be utilized as a novel agent in the treatment of fibrotic diseases.

The vicious cycle of frailty and pain: a two-sided causal relationship revealed.

Background: The decline in physiological functions in the older people is frequently accompanied with pain and frailty, yet the causal connection between frailty and pain remains uncertain. In this study, we utilized a two-sample Mendelian randomization (MR) approach to investigate the potential causal association between frailty and pain. Methods: Two-sample bidirectional MR was conducted using summary data from genome-wide association studies to examine the potential causal relationship between frailty (defined by the frailty index and frailty phenotype) and pain. Summary genome wide association statistics were extracted from populations of European ancestry. We also investigated the causal relationship between frailty and site-specific pain, including joint pain, limb pain, thoracic spine pain and low back pain. Causal effects were estimated using the inverse variance weighting method. Sensitivity analyses were performed to validate the robustness of the results. Results: Genetic predisposition to frailty was associated with an increased risk of pain (frailty phenotype odds ratio [OR]: 1.73; P = 3.54 × 10-6, frailty index OR: 1.36; P = 2.43 × 10-4). Meanwhile, individuals with a genetic inclination toward pain had a higher risk of developing frailty. Regarding site-specific pain, genetic prediction of the frailty phenotype increased the occurrence risk of joint pain, limb pain and low back pain. Reverse MR analysis further showed that limb pain and low back pain were associated with an increased risk of frailty occurrence. Conclusion: This study presented evidence supporting a bidirectional causal relationship between frailty and pain. We highlighted the significance of addressing pain to prevent frailty and recommend the inclusion of pain assessment in the evaluation system for frailty.