Low-mass Active Galactic Nuclei on the Fundamental Plane of Black Hole Activity

It is widely known that in active galactic nuclei (AGNs) and black hole X-ray binaries (BHXBs), there is a tight correlation among their radio luminosity ($L_R$), X-ray luminosity ($L_X$) and BH mass (\mbh), the so-called `fundamental plane' (FP) of BH activity. Yet the supporting data are very limited in the \mbh regime between stellar mass (i.e., BHXBs) and 10$^{6.5}$\,\msun\ (namely, the lower bound of supermassive BHs in common AGNs). In this work, we developed a new method to measure the 1.4 GHz flux directly from the images of the VLA FIRST survey, and apply it to the type-1 low-mass AGNs in the \cite{2012ApJ...755..167D} sample. As a result, we obtained 19 new low-mass AGNs for FP research with both \mbh\ estimates (\mbh \approx 10^{5.5-6.5}\,\msun), reliable X-ray measurements, and (candidate) radio detections, tripling the number of such candidate sources in the literature.Most (if not all) of the low-mass AGNs follow the standard radio/X-ray correlation and the universal FP relation fitted with the combined dataset of BHXBs and supermassive AGNs by \citet{2009ApJ...706..404G}; the consistency in the radio/X-ray correlation slope among those accretion systems supports the picture that the accretion and ejection (jet) processes are quite similar in all accretion systems of different \mbh. In view of the FP relation, we speculate that the radio loudness $\mathcal{R}$ (i.e., the luminosity ratio of the jet to the accretion disk) of AGNs depends not only on Eddington ratio, but probably also on \mbh.Comment: ApJ accepte

Antibiotics and antibiotic resistance genes in global lakes:A review and meta-analysis

Lakes are an important source of freshwater, containing nearly 90% of the liquid surface fresh water worldwide. Long retention times in lakes mean pollutants from discharges slowly circulate around the lakes and may lead to high ecological risk for ecosystem and human health. In recent decades, antibiotics and antibiotic resistance genes (ARGs) have been regarded as emerging pollutants. The occurrence and distribution of antibiotics and ARGs in global freshwater lakes are summarized to show the pollution level of antibiotics and ARGs and to identify some of the potential risks to ecosystem and human health. Fifty-seven antibiotics were reported at least once in the studied lakes. Our meta-analysis shows that sulfamethoxazole, sulfamerazine, sulfameter, tetracycline, oxytetracycline, erythromycin, and roxithromycin were found at high concentrations in both lake water and lake sediment. There is no significant difference in the concentration of sulfonamides in lake water from China and that from other countries worldwide; however, there was a significant difference in quinolones. Erythromycin had the lowest predicted hazardous concentration for 5% of the species (HC5) and the highest ecological risk in lakes. There was no significant difference in the concentration of sulfonamide resistance genes (sul1 and sul2) in lake water and river water. There is surprisingly limited research on the role of aquatic biota in propagation of ARGs in freshwater lakes. As an environment that is susceptible to cumulative build-up of pollutants, lakes provide an important environment to study the fate of antibiotics and transport of ARGs with a broad range of niches including bacterial community, aquatic plants and animals

Deficiencies of the Lipid-Signaling Enzymes Phospholipase D1 and D2 Alter Cytoskeletal Organization, Macrophage Phagocytosis, and Cytokine-Stimulated Neutrophil Recruitment

Cell migration and phagocytosis ensue from extracellular-initiated signaling cascades that orchestrate dynamic reorganization of the actin cytoskeleton. The reorganization is mediated by effector proteins recruited to the site of activity by locally-generated lipid second messengers. Phosphatidic acid (PA), a membrane phospholipid generated by multiple enzyme families including Phospholipase D (PLD), has been proposed to function in this role. Here, we show that macrophages prepared from mice lacking either of the classical PLD isoforms PLD1 or PLD2, or wild-type macrophages whose PLD activity has been pharmacologically inhibited, display isoform-specific actin cytoskeleton abnormalities that likely underlie decreases observed in phagocytic capacity. Unexpectedly, PA continued to be detected on the phagosome in the absence of either isoform and even when all PLD activity was eliminated. However, a disorganized phagocytic cup was observed as visualized by imaging PA, F-actin, Rac1, an organizer of the F-actin network, and DOCK2, a Rac1 activator, suggesting that PLD-mediated PA production during phagocytosis is specifically critical for the integrity of the process. The abnormal F-actin reorganization additionally impacted neutrophil migration and extravasation from the vasculature into interstitial tissues. Although both PLD1 and PLD2 were important in these processes, we also observed isoform-specific functions. PLD1-driven processes in particular were observed to be critical in transmigration of macrophages exiting the vasculature during immune responses such as those seen in acute pancreatitis or irritant-induced skin vascularization

Flexoelectricity-stabilized ferroelectric phase with enhanced reliability in ultrathin La:HfO2 films

Doped HfO2 thin films exhibit robust ferroelectric properties even for nanometric thicknesses, are compatible with current Si technology and thus have great potential for the revival of integrated ferroelectrics. Phase control and reliability are core issues for their applications. Here we show that, in (111)-oriented 5%La:HfO2 (HLO) epitaxial thin films deposited on (La0.3Sr0.7)(Al0.65Ta0.35)O3 substrates, the flexoelectric effect, arising from the strain gradient along the films normal, induces a rhombohedral distortion in the otherwise Pca21 orthorhombic structure. Density functional calculations reveal that the distorted structure is indeed more stable than the pure Pca21 structure, when applying an electric field mimicking the flexoelectric field. This rhombohedral distortion greatly improves the fatigue endurance of HLO thin films by further stabilizing the metastable ferroelectric phase against the transition to the thermodynamically stable non-polar monoclinic phase during repetitive cycling. Our results demonstrate that the flexoelectric effect, though negligibly weak in bulk, is crucial to optimize the structure and properties of doped HfO2 thin films with nanometric thicknesses for integrated ferroelectric applications

Integrated Serum and Fecal Metabolomics Study of Collagen-Induced Arthritis Rats and the Therapeutic Effects of the Zushima Tablet

The Zushima tablet (ZT) has been used for decades in the clinical treatment of rheumatoid arthritis (RA) in China. However, its therapeutic mechanism is unclear. In this study, we aimed to explore the distinctive metabolic patterns in collagen-induced arthritis (CIA) rats and evaluate the therapeutic effects of ZT on RA using untargeted serum and fecal metabolomics approaches based on gas chromatography coupled with mass spectrometry. Body weight, hind paw swelling, TNF-α and IL-1β levels, arthritis scores, and histopathological parameters were assessed. In the metabolomics study, 31 altered metabolites in the serum and 30 in the feces were identified by comparing the model with the control group using statistical processing. These altered metabolites revealed that the tricarboxylic acid cycle, glycolysis metabolism, fatty acid metabolism, and purine metabolism were disturbed in CIA rats, and most of these altered metabolites including l-isoleucine, l-aspartic acid, pyruvic acid, cholic acid, and hypoxanthine, were rectified by ZT. Furthermore, short-chain fatty acids in feces were quantitatively determined, and the results showed that ZT could regulate the levels of propionate, butyrate, and valerate in CIA rats. Then, gut microbiota were analyzed by 16S rRNA analysis. Our results showed that Firmicutes and Bacteroidetes were the most abundant bacteria in rats. The levels of 19 types of bacteria at the family level were altered in RA rats, and most of them could be regulated by ZT. This study demonstrated that metabolomics analysis is a powerful tool for providing novel insight into RA and for elucidating the potential mechanism of ZT

Improving the stability and transdermal permeability of phycocyanin loaded cubosomes

Instability and low transdermal permeability of protein antioxidants are major obstacles to resist oxidative stress in transdermal drug delivery system. To overcome these shortcomings, cubosomes were developed as an advanced transdermal delivery system to improve stability and transdermal absorption of the model antioxidant phycocyanin in this study. Glyceryl monooleate and poloxamer 407 (P407) were used to prepare cubosomes as carrier matrix and stabilizer, respectively. Phycocyanin loaded cubosomes (PC-cubosomes) were prepared by the emulsification and homogenization method. A 33 full factorial design was used to optimize the cubosome formulations. The final optimal PC-cubosomes possessed an average particle size of 183.2 ± 0.5 nm and a negative surface charge as well as achieved a high encapsulation efficiency of 87.2% ± 2.7%. PC-cubosomes appeared as nano-sized and well-shaped spheres with highly ordered cubical structures. The residual amount of phycocyanin in PC-cubosomes was 3-fold higher than that in the free drug solution after 10 days ultraviolet radiation exposure. In vitro release kinetics of phycocyanin from PC-cubosomes fitted to the Higuchi kinetic model, indicating that phycocyanin released from cubosomes mainly attributed to drug diffusion and dissolution. PC-cubosomes also exhibited higher permeability (39.79 μg⋅cm−2⋅hour−1) across the rat skin than phycocyanin solution (16.33 μg⋅cm−2⋅hour−1). Furthermore, PC-cubosomes were easily taken up by keratinocytes, thereby achieving a prolonged anti-oxidative stress effect. These results therefore suggested that cubosomes could be a promising transdermal delivery system to improve the stability and transdermal permeability of phycocyanin

MiR-27b-3p Inhibition Enhances Browning of Epididymal Fat in High-Fat Diet Induced Obese Mice

Objective: Long-term dysregulation of energy balance is the key component of the obesity epidemic. Given the harm of central obesity and the discovery that beige cells appear within white adipose tissue (WAT), enhancing the energy-expending or “browning” ability of visceral adipose tissue (VAT) has become of therapeutic interest. In this study, we focused on the regulating role of microRNA (miRNA)-27b-3p in mice epididymal white adipose tissue (eWAT) browning.Methods: High-fat diet (HFD) induced obese mice model was constructed. Expression of miR-27b-3p and Ucp1 in eWAT was measured during the course of HFD. Through tail vein injection of antimiR-27b-3p, miR-27b-3p expression was inhibited to analyze the potential role of miR-27b-3p in fat browning and metabolism.Results: miR-27b-3p was predominantly expressed in eWAT and browning ability of eWAT in HFD induced obese mice was impaired. Inhibition of miR-27b-3p enhanced browning capacity of eWAT in mice fed an HFD and led to weight loss and insulin sensitivity improvement.Conclusions: High expression of miR-27b-3p in eWAT inhibits browning ability and leads to visceral fat accumulation. It is suggested miR-27b-3p may become a potential therapeutic option for visceral obesity and its associated diseases

Exploration of risk factors and characteristics of COVID-19 infection among patients with hematological malignancies in Suzhou, China: a retrospective study

Background and aimPatients diagnosed with cancer, particularly those with hematologic malignancies, frequently exhibit a state of immunosuppression. Currently, there remains a scarcity of dependable biomarkers for assessing the severity of COVID-19 in individuals with hematologic malignancies. We conducted a retrospective study of morbidity and mortality in patients with hematological malignancies (HM) who had contracted COVID-19. The aim was to offer a reference for clinical diagnosis and treatment.MethodsA total of 71 patients with HM-confirmed COVID-19 were enrolled from December 2022 to May 2023. Clinical symptoms, laboratory findings, and treatment approaches were collected and documented. Patients were classified into survival and death groups based on their COVID-19 outcomes, and statistical analysis was performed on the clinical data from both groups.ResultsAmong the 71 patients, 57 (80.3%) were alive, and 14 (19.7%) had died. The mean age of patients in the death group was significantly higher than that of the survival group (51.29 ± 20.76 vs. 49.47 ± 13.04, P=0.030). The proportion of patients receiving mechanical ventilation was significantly higher in the death group (P<0.001). The mortality rate was significantly higher in the critically severe group compared to the mild, moderate, and severe groups (P<0.001). Correlation analysis revealed that certain laboratory indicators lactic acid dehydrogenase (LDH), albumin (ALB), creatine kinase (CK), troponin T (TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP) and fibrin degradation product (FDP), which exhibited significant differences between groups, were significantly correlated with COVID-19-related mortality (all P<0.05). The Cox proportional hazards model indicated that LDH was an independent risk factor associated with the prognosis of HM-confirmed COVID-19.ConclusionPatients with hematologic malignancies suffer severe morbidity and mortality due to COVID-19 infection. LDH may serve as a risk factor associated with prognosis in the treatment of COVID-19. Monitoring variations in LDH levels can assist healthcare providers in evaluating disease progression, adjusting treatment plans in a timely manner, and predicting patient outcomes

A highly potent antibody effective against SARS-CoV-2 variants of concern.

Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals