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Motivated by entanglement protection, our work utilizes a resonance effect to enhance optomechanical entanglement in the coherent-state representation. We propose a filtering model to filter out the highly frequency-detuned coupling components between a thermal-mechanical mode and its surrounding heat baths within the weak-coupling limit. We reveal that continuous-variable entanglement protection involves the elimination of degrees of freedom associated with significant detuning components, thereby resisting decoherence. We construct a nonlinear Langevin equation of the filtering model and numerically show that the filtering model doubles the robustness of a stationary maximum optomechanical entanglement with respect to thermal noise and mechanical damping. Furthermore, we generalize these results to an optical cavity array with one oscillating end-mirror to investigate the long-distance optimal optomechanical entanglement transfer. Our study breaks new ground for applying the resonance effect to protect the quantum system from decoherence and advancing the possibilities for large-scale quantum information processing and quantum network construction., Comment: 19 pages, 7 figures

We derive a compact analytical solution of the $n$th-order equal-time correlation functions by using the scattering matrix (S-matrix) under a weak coherent state input. Our solution applies to any dissipative quantum system that satisfies the U(1) symmetry. We further extend our analytical solution into two categories depending on whether the input and output channels are identical. The first category provides a new path for studying cross-correlation and multiple drives cases, while the second category is instrumental in studying waveguide quantum electrodynamics systems. Our analytical solution allows for easy investigation of the statistical properties of multiple photons even in complex systems. Furthermore, we have developed a user-friendly open-source library in Python known as the quantum correlation solver, and this tool provides a convenient means to study various dissipative quantum systems that satisfy the abovementioned criterion. Our study breaks new ground for using the S-matrix to study the photonic correlation and advance the possibilities for exploring complex systems., 20 pages, 8 figures, the QCS open-source library is available at http://github.com/ZhiGuangLu/qcs/

High-entropy alloy (HEA) nanocrystals have attracted extensive attention in catalysis. However, there are no effective strategies for synthesizing them in a controllable and predictable manner. With quinary HEA nanocrystals made of platinum-group metals as an example, we demonstrate that their structures with spatial compositions can be predicted by quantitatively knowing the reduction kinetics of metal precursors and entropy of mixing in the nanocrystals under dropwise addition of the mixing five–metal precursor solution. The time to reach a steady state for each precursor plays a pivotal role in determining the structures of HEA nanocrystals with homogeneous alloy and core-shell features. Compared to the commercial platinum/carbon and phase-separated counterparts, the dendritic HEA nanocrystals with a defect-rich surface show substantial enhancement in catalytic activity and durability toward both hydrogen evolution and oxidation. This quantitative study will lead to a paradigm shift in the design of HEA nanocrystals, pushing away from the trial-and-error approach.

Li$_x$CoO$_2$ based batteries have serious capacity degradation and safety issues when cycling at high-delithiation states but full and consistent mechanisms are still poorly understood. Herein, a global neural network potential (GNNP) is developed to provide direct theoretical understandings by performing long-time and large-size atomic simulations. We propose a self-consistent picture as follows: (i) CoO$_2$ layers are easier to glide with longer distances at more highly delithiated states, resulting in structural transitions and structural inhomogeneity; (ii) at regions between different phases with different Li distributions due to gliding, local strains are induced and accumulate during cycling processes; (3) accumulated strains cause the rupture of Li diffusion channels and result in formation of oxygen dimers during cycling especially when Li has inhomogeneous distributions, leading to capacity degradations and safety issues. We find that large tensile strains combined with inhomogeneous distributions of Li ions play critical roles in the formation processes of blocked Li diffusion channels and the oxygen dimers at high-delithiation states, which could be the fundamental origins of capacity degradations and safety issues. Correspondingly, suppressing accumulations of strains by controlling charge and discharge conditions as well as suppressing the gliding will be helpful for improving the performance of lithium-ion batteries (LIBs)., 17 pages, 5 figures, 1 table

Objective Summarize the clinical characteristics and treatment plan of 2 cases of abnormal anastomosis at the origin of the posterior inferior cerebellar artery (PICA) complicated with aneurysm. Methods and Results Two cases of abnormal anastomosis of the PICA complicated with aneurysms all showed spontaneous subarachnoid hemorrhage (SAH). MRI showed abnormal anastomosis of the PICA, accompanied by multiple small aneurysms at the anastomotic vessel or anastomotic site. All patients underwent occipital artery (OA)⁃PICA bypass graft and electrocoagulation of the aneurysms at the same time. Use "PICA anastomosis" as the key words to search PubMed (January 1, 2000 to June 30, 2021) 8 articles in English, 8 patients, combined with 2 cases in this article cases, a total of 10 patients with abnormal anastomosis at the origin of the PICA complicated with aneurysm. All cases occurred as spontaneous SAH; 8 cases of aneurysms occurred at the anastomosis site, one case occurred at the distal end of the PICA, and one case occurred in a branch of the original artery. Five cases underwent craniotomy, 3 cases of OA⁃PICA bypass surgery and concurrent electrocoagulation (2 cases) or clipping (one case) of the aneurysms, one case of simple aneurysm clipping, and one case of aneurysm clipping combined with cutting off anastomotic artery, and there were no clear complications after surgery; 4 cases underwent endovascular interventional treatment, 2 cases of coil embolization of aneurysms, 2 cases of Glubran glue embolization of aneurysms, of which 3 cases had postoperative complications, manifested as mild brainstem infarction (2 cases) or disturbance of consciousness (one case). Conclusions Abnormal anastomosis at the origin of the PICA complicated with aneurysm is rare, and the risk of rupture and hemorrhage is high. OA⁃PICA bypass and electrocoagulation or clipping of the aneurysm can be used as a treatment option.

Collision-induced dissociation (CID) tandem mass spectrometry is commonly used for carbohydrate structural determinations. In the CID tandem mass spectrometry approach, carbohydrates are dissociated into fragments, and this is followed by the structural identification of fragments through subsequent CID. The success of the structural analysis depends on the structural correlation of fragments before and after dissociation, that is, structural memory of fragments. Fragments that completely lose the memory of their original structures cannot be used for structural analysis. By contrast, fragments with extremely strong correlations between the structures before and after fragmentation retain the information on their original structures as well as have memories of their precursors' entire structures. The CID spectra of these fragments depend on their own structures and on the remaining parts of the precursor structures, making structural analysis impractical. For effective structural analysis, the fragments produced from a precursor must have good structural memory, meaning that the structures of these fragments retain their original structure, and they must not be strongly affected by the remaining parts of the precursors. In this study, we found that most of the carbohydrate fragments produced by low-energy CID have good memory in terms of linkage position and anomericity. Fragments with ugly memory, where fragment structures change with the remaining parts of the precursors, can be attributed to C ion formation in a linear form. Fragments with ugly memory can be changed to have good memory by preventing linear C ion generation by using an alternative CID sequence, or the fragments of ugly memory can become useful in structural analysis when the contribution of linear C ions in fragmentation patterns is understood.

A convenient route for the preparation of l-gulose and its C-6 derivatives starting from commercially available 2,3:5,6-diisopropylidene-d-mannofuranose via C-5 epimerization as the key step was developed. 1-O-Benzylation followed by regioselective hydrolysis of the 5,6-isopropylidene group furnished benzyl 2,3-isopropylidene-α-d-mannofuranoside, which was subjected upon regioselective one-pot 6-O-benzoylation and 5-O-mesylation, providing the corresponding 5-OMs-6-OBz derivative in excellent selectivity. Treatment of this mesylate compound with potassium t-butoxide to remove the benzoyl group followed by intramolecular S

The extracellular human endo-6-O-sulfatases (Sulf-1 and Sulf-2) are responsible for the endolytic cleavage of the 6-sulfate groups from the internal D-glucosamine residues in the highly sulfated subdomains of heparan sulfate proteoglycans. A trisaccharide sulfate, IdoA2OS-GlcNS6S-IdoA2OS, was identified as the minimal size of substrate for Sulf-1. In order to study the complex structure with Sulf-1 for developing potential drugs, two trisaccharide analogs, IdoA2OS-GlcNS6OSO2NH2-IdoA2OS-OMe and IdoA2OS-GlcNS6NS-IdoA2OS-OMe, were rationally designed and synthesized as the Sulf-1 inhibitors with IC50 values at 0.27 and 4.6 μM, respectively.

Free oligosaccharides are abundant macronutrients in milk and involved in prebiotic functions and antiadhesive binding of viruses and pathogenic bacteria to colonocytes. Despite the importance of these oligosaccharides, structural determination of oligosaccharides is challenging, and milk oligosaccharide biosynthetic pathways remain unclear. Oligosaccharide structures are conventionally determined using a combination of chemical reactions, exoglycosidase digestion, nuclear magnetic resonance spectroscopy, and mass spectrometry. Most reported free oligosaccharides are highly abundant and have lactose at the reducing end, and current oligosaccharide biosynthetic pathways in human milk are proposed based on these oligosaccharides. In this study, a new mass spectrometry technique, which can identify linkages, anomericities, and stereoisomers, was applied to determine the structures of free oligosaccharides in human, bovine, and caprine milk. Oligosaccharides that do not follow the current biosynthetic pathways and are not synthesized by any discovered enzymes were found, indicating the existence of undiscovered biosynthetic pathways and enzymes.

Remdesivir, an inhibitor of RNA-dependent RNA polymerase developed by Gilead Sciences, has been used for the treatment of COVID-19. The synthesis of remdesivir is, however, challenging, and the overall cost is relatively high. Particularly, the stereoselective assembly of the P-chirogenic center requires recrystallization of a 1:1 isomeric p-nitrophenylphosphoramidate mixture several times to obtain the desired diastereoisomer (39%) for further coupling with the d-ribose-derived 5-alcohol. To address this problem, a variety of chiral bicyclic imidazoles were synthesized as organocatalysts for stereoselective (S)-P-phosphoramidation employing a 1:1 diastereomeric mixture of phosphoramidoyl chloridates as the coupling reagent to avoid a waste of the other diastereomer. Through a systematic study of different catalysts at different temperatures and concentrations, a mixture of the (S)- and (R)-P-phosphoramidates was obtained in 97% yield with a 96.1/3.9 ratio when 20 mol % of the chiral imidazole-cinnamaldehyde-derived carbamate was utilized in the reaction at -20 °C. A 10-g scale one-pot synthesis via a combination of (S)-P-phosphoramidation and protecting group removal followed by one-step recrystallization gave remdesivir in 70% yield and 99.3/0.7 d.r. The organocatalyst was recovered in 83% yield for reuse, and similar results were obtained. This one-pot process offers an excellent opportunity for industrial production of remdesivir.

To improve the mechanical properties of a sintered WHA using high entropy alloy as the matrix (W-HEA), investigations were carried out to apply deformation strengthening method of hot swaging on the W-HEA. The W-HEA samples were swaged around 1300°C with the 10%, 15% and 20% of reduction in area. The results show that the strength and hardness of the W-HEA composite increased with the increasing degree of deformation. And the aspect ratio of tungsten grains increases along the axial direction in the swaged alloys. The hardness of W-HEA with a 20% reduction in area reaches 448 HV, and the dynamic compression yield strength is about 1911 MPa. After hot swaging, the hardness and strength of the W-HEA are greatly improved compared with the sintered W-HEA.

The incidence of central nervous system (CNS) diseases is increasing with the aging population. However, it remains challenging to deliver drugs into the CNS because of the existence of a blood-brain barrier (BBB). Notably, rabies virus glycoprotein (RVG) peptides have been developed as delivery ligands for CNS diseases. So far, massive RVG peptide modified carriers have been reported, such as liposomes, micelles, polymers, exosomes, dendrimers, and proteins. Moreover, these drug delivery systems can encapsulate almost all small molecules and macromolecule drugs, including siRNA, microRNAs, DNA, proteins, and other nanoparticles, to treat various CNS diseases with efficient and safe drugs. In this review, targeted delivery systems with RVG peptide modified carriers possessing favorable biocompatibility and delivery efficiency are summarized.

Random lasers exhibit many exotic properties, including chaotic behavior, light localization, broad angular emission, and cost-effective fabrication, which enable them to attract both scientific and industrial interests. However, before the realization of their potential applications, several challenges still remain including the underlying mechanism and controllability due to their inherent multidirectional and chaotic fluctuations. Through more than two decades of collaborative efforts, the discovery of Anderson localization in random lasers provides a plausible route to resolve the difficulties, which enables one to tailor the number of lasing modes and stabilize the emission spectra. However, the related studies are rather rare and only restricted to limited wavelengths. In this study, based on enhanced Anderson localization assisted by surface plasmon resonance, spectrally stable deep-ultraviolet lasing action in AlGaN multiple quantum wells (MQWs) is demonstrated. Our work serves as firm evidence to demonstrate the underlying mechanism of stabilized deep-ultraviolet random laser action that multiple scattering of a light beam in a disordered medium can induce Anderson localization similar to electron behavior. This feature covers the whole spectral range, and it is a universal phenomenon of an electromagnetic wave. Notably, stabilized deep-ultraviolet random laser action has not been demonstrated in all previous studies, even though it has great academic interest and potential application in many areas from environmental protection to biomedical engineering.

The extracellular human endo-6

International audience; Dysregulation of amyloidogenic proteins and their abnormal processing and deposition in tissues cause systemic and localized amyloidosis. Formation of amyloid β (Aβ) fibrils that deposit as amyloid plaques in Alzheimer's disease (AD) brains is an earliest pathological hallmark. The polysulfated heparan sulfate (HS)/heparin (HP) is one of the non-protein components of Aβ deposits that not only modulates Aβ aggregation, but also acts as a receptor for Aβ fibrils to mediate their cytotoxicity. Interfering with the interaction between HS/HP and Aβ could be a therapeutic strategy to arrest amyloidosis. Here we have synthesized the 6-O-phosphorylated HS/HP oligosaccharides and reported their competitive effects on the inhibition of HP-mediated Aβ fibril formation in vitro using a thioflavin T fluorescence assay and a tapping mode atomic force microscopy.

Individual interactions between glycans and their receptors are usually weak, although these weak interactions can combine to realize a strong interaction (multivalency). Such multivalency plays a crucial role in the recognition of host cells by pathogens. Glycodendrimers are useful materials for the reconstruction of this multivalent interaction. However, the introduction of a large number of glycans to a dendrimer core is fraught with difficulties. We herein synthesized antipathogenic glycodendrimers using the self-activating click chemistry (SACC) method developed by our group. The excellent reactivity of SACC enabled the efficient preparation of sialyl glycan and Gb3 glycan dendrimers, which exhibited strong avidity toward hemagglutinin on influenza virus and Shiga toxin B subunit produced by Escherichia coli, respectively. We demonstrated the usefulness of SACC-based glycodendrimers as antipathogenic compounds.

The spectral specificity of deep-ultraviolet (UV) photodetectors makes them useful in many fields, spanning from disinfection of various surfaces and water purification to optical communication. As...

Light emitting diodes (LEDs) are ubiquitous in our daily life nowadays. Among them, ultraviolet LEDs are unique because of their wide range of potential applications, spanning from biomedicine, env...

Human endo-O-sulfatases (Sulf-1 and Sulf-2) are extracellular heparan sulfate proteoglycan (HSPG)-specific 6-O-endosulfatases, which regulate a multitude of cell-signaling events through heparan sulfate (HS)-protein interactions and are associated with the onset of osteoarthritis. These endo-O-sulfatases are transported onto the cell surface to liberate the 6-sulfate groups from the internal d-glucosamine residues in the highly sulfated subdomains of HSPGs. In this study, a variety of HS oligosaccharides with different chain lengths and N- and O-sulfation patterns via chemical synthesis were systematically studied about the substrate specificity of human Sulf-1 employing the fluorogenic substrate 4-methylumbelliferyl sulfate (4-MUS) in a competition assay. The trisaccharide sulfate IdoA2S-GlcNS6S-IdoA2S was found to be the minimal-size substrate for Sulf-1, and substitution of the sulfate group at the 6-O position of the d-glucosamine unit with the sulfonamide motif effectively inhibited the Sulf-1 activity with IC50 = 0.53 μM, Ki = 0.36 μM, and KD = 12 nM.

Hyaluronic acid (HA) is a ubiquitous glycosaminoglycan in the extracellular matrix and a ligand of CD44, a transmembrane glycoprotein that is important in cell migration. Crystal and NMR studies found a hexasaccharide of the pattern (GlcA-GlcNAc)3 as the shortest HA that could bind to CD44, but molecular dynamics simulations indicated that a tetrasaccharide of the pattern (GlcNAc-GlcA)2 is the key structure interacting with CD44. Access to oligomers with such a repeat pattern is crucial in binding studies with CD44. Here we developed a synthetic procedure to afford the HA oligosaccharides with the GlcNAc-GlcA repeating unit and measured the binding interaction between these sugars and human CD44 by isothermal titration calorimetry (ITC). During the chemical synthesis, we successfully generated the β-glycosidic bond in the absence of neighbouring group participation and overcome the issues in the oxidation step. In addition, ammonia-free dissolving metal reduction for debenzylation and azido reduction has been applied in carbohydrate synthesis for the first time. ITC analysis revealed that the HA tetrasaccharide (GlcNAc-GlcA)2 could indeed interact and bind to the human CD44.

Free oligosaccharides are abundant macronutrients in milk and involved in prebiotic functions and antiadhesive binding of pathogenic bacteria to colonocytes. Despite the importance of these oligosaccharides, structural determination of oligosaccharides is challenging, and milk oligosaccharide biosynthetic pathways remain unclear. Oligosaccharide structures are conventionally determined using a combination of chemical reactions, exoglycosidase digestion, nuclear magnetic resonance spectroscopy, and mass spectrometry. Most reported free oligosaccharides are highly abundant and have lactose at the reducing end, and current oligosaccharide biosynthetic pathways in human milk are proposed based on these oligosaccharides. In this study, a new mass spectrometry technique, which can identify linkages, anomericities, and stereoisomers, was applied to determine the structures of free oligosaccharides in human, bovine, and caprine milk. Oligosaccharides that do not follow the current biosynthetic pathways and are not synthesized by any discovered enzymes were found, indicating the existence of undiscovered biosynthetic pathways and enzymes. New biosynthetic pathways were proposed.

To review and analyze the trend of researches on prostatitis in China in the past two decades.We searched the core collection of China National Knowledge Infrastructure (CNKI) for studies on prostatitis, and analyzed the data obtained using Excel, Citespace and VOSviewer.Totally, 1 216 original articles were identified, with 3 271 keywords, ≥3-time high-frequency keywords accounting for 12.9%, with "", "", "chronic prostatitis", "prostatitis", and "" as the top 5 ones, each with a centrality higher than 300. Major prostatitis-related studies focused on the 8 keywords, namely, prostatitis, prostatic fluid, rats, prostate, syndromes, efficacy observation, compound (in traditional Chinese medicine, TCM), and therapeutic application. The included literature involved 2 808 authors, with 402 involved more than twice and most of them in a scattered manner. The major topics of prostatitis studies varied in the past two decades, focusing on TCM therapies, promotion of blood circulation and stasis and comprehensive nursing in 2000－2001, on animal models, CD4+ lymphocytes and other experimental molecules in 2007－2010, on urodynamics, risk factors and specific antigens in 2013－2016, and on literature information resources in 2016.The immune mechanism remains a hot topic in the future researches on prostatitis. In terms of treatment of the disease, TCM has a potential value, and more practice and studies are required for an optimal combination of TCM and Western medicine. Strengthened collaborative efforts are needed to establish an authoritative source channel for the keywords, and incorporate it into the national standard system, and above all, to integrate the prostatitis study into multi-disciplinary researches, eliminate academic barriers, encourage collaborative innovation with multiple parties, and promote the exchanges and development in this field.

Receptor activator of nuclear factor-κB ligand (RANKL) has been found to induce osteoclastogenesis and bone resorption. However, the underlying molecular mechanisms remain unclear. Via conducting a series of biochemical experiments with in vitro cell lines, this study investigated the role and mechanism of NADPH oxidase 4 (Nox4) in RANKL-induced autophagy and osteoclastogenesis. In the current study, we found that RANKL dramatically induced autophagy and osteoclastogenesis, inhibition of autophagy with chloroquine (CQ) markedly attenuates RANKL-induced osteoclastogenesis. Interestingly, we found that the protein level of Nox4 was remarkably upregulated by RANKL treatment. Inhibition of Nox4 by 5-O-methyl quercetin or knockdown of Nox4 with specific shRNA markedly attenuated RANKL-induced autophagy and osteoclastogenesis. Furthermore, we found that Nox4 stimulated the production of nonmitochondrial reactive oxygen species (ROS), activating the critical unfolded protein response (UPR)-related signaling pathway PERK/eIF-2α/ATF4, leading to RANKL-induced autophagy and osteoclastogenesis. Blocking the activation of PERK/eIF-2α/ATF4 signaling pathway either by Nox4 shRNA, ROS scavenger (NAC) or PERK inhibitor (GSK2606414) significantly inhibited autophagy during RANKL-induced osteoclastogenesis. Collectively, this study reveals that Nox4 promotes RANKL-induced autophagy and osteoclastogenesis via activating ROS/PERK/eIF-2α/ATF4 pathway, suggesting that the pathway may be a novel potential therapeutic target for osteoclastogenesis-related disease.

Objective— PAR4 (protease-activated receptor 4), one of the thrombin receptors in human platelets, has emerged as a promising target for the treatment of arterial thrombotic disease. Previous studies implied that thrombin exosite II, known as a binding site for heparin, may be involved in thrombin-induced PAR4 activation. In the present study, a heparin octasaccharide analog containing the thrombin exosite II–binding domain of heparin was chemically synthesized and investigated for anti-PAR4 effect. Approach and Results— PAR4-mediated platelet aggregation was examined using either thrombin in the presence of a PAR1 antagonist or γ-thrombin, which selectively activates PAR4. SCH-28 specifically inhibits PAR4-mediated platelet aggregation, as well as the signaling events downstream of PAR4 in response to thrombin. Moreover, SCH-28 prevents thrombin-induced β-arrestin recruitment to PAR4 but not PAR1 in Chinese Hamster Ovary-K1 cells using a commercial enzymatic complementation assay. Compared with heparin, SCH-28 is more potent in inhibiting PAR4-mediated platelet aggregation but has no significant anticoagulant activity. In an in vitro thrombosis model, SCH-28 reduces thrombus formation under whole blood arterial flow conditions. Conclusions— SCH-28, a synthetic small-molecular and nonanticoagulant heparin analog, inhibits thrombin-induced PAR4 activation by interfering with thrombin exosite II, a mechanism of action distinct from other PAR4 inhibitors that target the receptor. The characteristics of SCH-28 provide a new strategy for targeting PAR4 with the potential for the treatment of arterial thrombosis.

Most lung cancer bone metastasis are characterized by osteolytic destruction and osteoblastic activity is significantly decreased, suggesting that hypoxia may play a critical role in the process, but the underlying mechanisms remain unknown. Semaphorin 4D (Sema4D) is a recently discovered osteogenic inhibitory factor that is expressed at high levels in lung cancers. Here, CoCl2-induced hypoxia significantly enhanced the inhibitory effect of lung cancer cell conditioned media on osteoblast differentiation by inducing the expression and secretion of Sema4D in a HIF-1α- but not HIF-2α-dependent manner. Moreover, HIF-1α directly regulated Sema4D expression by binding to bases 1171 to 798 in the Sema4D promoter. Furthermore, hypoxia increased Sema4D secretion by upregulating a disintegrin and metalloproteinase 17 (ADAM17) expression in lung cancer in a HIF-1α-dependent manner. In bone metastasis samples from 49 patients with lung cancer, Sema4D and ADAM17 expression significantly correlated with HIF-1α expression and strongly correlated with a poor differentiation status and osteolytic bone destruction. These results provide the first evidence that HIF-1α-induced Sema4D expression and secretion play important roles in lung cancer osteolytic bone metastasis by inhibiting osteoblast differentiation, thereby providing potential strategies for the treatment of bone metastasis via targeting osteoblasts.

The influenza A (InfA) virus, which poses a significant global public health threat, is routinely classified into "subtypes" based on viral hemagglutinin (HA) and neuraminidase (NA) antigens. Because there are nearly 200 viral subtypes, current diagnostic approaches require multiplexing or array systems to cover various subtypes of HA and NA. A microfluidic chip featuring a HA × NA array was consequently developed herein for diagnosis and subtyping of InfA viruses via the use of glycan-coated magnetic beads followed by reverse transcription (RT) polymerase chain reaction (PCR). Up to 12 InfA subtypes were simultaneously detected in an automated fashion in less than 100 minutes on this microfluidic platform, representing a significant improvement in analysis speed compared to benchtop RT-PCR and chip-based microarray systems. The limits of detection of the RT-PCR assays ranged from 40 to 3000 copy numbers for the different subtypes of InfA viruses, around two orders of magnitude higher than in previous studies using microfluidic technologies. In summary, the array-type microfluidic chip system provides a rapid, sensitive, and fully automated approach for detection and multiple subtyping of InfA.

A hybrid software defined networks (SDN) network contains both traditional and SDN network, which combines the robustness of traditional protocols with the flexibility of SDN while avoiding their limitations and incompatibility. However, a hybrid SDN network comes with its own set of challenges, including error-prone deployment processes, risks of inconsistency, and complex incremental deployment strategies. In this paper, we present a survey of the deployment solutions and optimization strategies for hybrid SDN networks. We systematically review solutions to control plane and data plane deployments, and describe typical use cases of hybrid SDN networks. We discuss and compare various optimization strategies from perspectives of traffic engineering, resource saving, network control capacity, and network security. This paper aims to provide insights to researchers into the future development of hybrid SDN networks and inspire more efforts in this area.

Remdesivir, an inhibitor of RNA-dependent RNA polymerase developed by Gilead Sciences, has been used for the treatment of COVID-19. The synthesis of remdesivir is, however, challenging, and the overall cost is relatively high. Particularly, the stereoselective assembly of the P-chirogenic center requires recrystallization of a 1:1 isomeric

Significance COVID-19 is a global pandemic currently lacking an effective cure. We used a cell-based infection assay to screen more than 3,000 agents used in humans and animals and identified 15 with antiinfective activity, ranging from 0.1 nM to 50 μM. We then used in vitro enzymatic assays combined with computer modeling to confirm the activity of those against the viral protease and RNA polymerase. In addition, several herbal medicines were found active in the cell-based infection assay. To further evaluate the efficacy of these promising compounds in animal models, we developed a challenge assay with hamsters and found that mefloquine, nelfinavir, and extracts of Ganoderma lucidum (RF3), Perilla frutescens, and Mentha haplocalyx were effective against SARS-CoV-2 infection., The outbreak of COVID-19 caused by SARS-CoV-2 has resulted in more than 50 million confirmed cases and over 1 million deaths worldwide as of November 2020. Currently, there are no effective antivirals approved by the Food and Drug Administration to contain this pandemic except the antiviral agent remdesivir. In addition, the trimeric spike protein on the viral surface is highly glycosylated and almost 200,000 variants with mutations at more than 1,000 positions in its 1,273 amino acid sequence were reported, posing a major challenge in the development of antibodies and vaccines. It is therefore urgently needed to have alternative and timely treatments for the disease. In this study, we used a cell-based infection assay to screen more than 3,000 agents used in humans and animals, including 2,855 small molecules and 190 traditional herbal medicines, and identified 15 active small molecules in concentrations ranging from 0.1 nM to 50 μM. Two enzymatic assays, along with molecular modeling, were then developed to confirm those targeting the virus 3CL protease and the RNA-dependent RNA polymerase. Several water extracts of herbal medicines were active in the cell-based assay and could be further developed as plant-derived anti–SARS-CoV-2 agents. Some of the active compounds identified in the screen were further tested in vivo, and it was found that mefloquine, nelfinavir, and extracts of Ganoderma lucidum (RF3), Perilla frutescens, and Mentha haplocalyx were effective in a challenge study using hamsters as disease model.

Cholangiocarcinoma (CCA) is a lethal disease owing to its difficulty to be diagnosed at early stages and lack of effective treatment. To improve the accuracy of early diagnosis of CCA, one of the promising approaches is to use CCA-specific affinity reagents to detect CCA cells by liquid biopsy. In this study, bile juice, a body fluid close to lesions, was used as a clinical sample for CCA cell isolation and detection. Moreover, a novel microfluidic chip was designed and fabricated to detect CCA cells in the bile juice by using three types of affinity reagents. Experimental results showed that the three affinity reagents could capture CCA tumor cells in patients’ bile juice (with a volume of only 3 mL) within 120 min. This microfluidic system may serve as a promising tool for detecting CCA in clinical settings.

Malignant pleural mesothelioma (MPM) is a type of cancer originating from the pleura with high aggressiveness and poor prognosis. A timely diagnosis is crucial to improve its prognosis. Laboratory biomarkers have significant advantages of reduced invasiveness, low cost, and are observer‐independent, and therefore represent a promising diagnostic tool for MPM. MicroRNA is a family of non‐coding RNA that regulates gene expression at the post‐transcriptional level. Accumulated studies showed that microRNA, either in tissue, circulating, and body fluid, has potential diagnostic value for various disorders. Here, we reviewed the diagnostic value of microRNA for MPM., Malignant pleural mesothelioma (MPM) is a type of cancer originating from the pleura with high aggressiveness and poor prognosis, Laboratory biomarkers have significant advantages of reduced invasiveness, low cost, and are observer‐independent, and therefore represent a promising diagnostic tool for MPM. Here, we reviewed the diagnostic value of microRNA for MPM.

Background: Whether routine urinary analysis has a net benefit for urinary tract infection (UTI) screening is unclear. Methods: Using the laboratory information system (LIS), we retrospectively extracted the data of urine culture and routine analysis between January 2017 and April 2017. Receiver operating characteristic (ROC) curve, logistic regression model, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to estimate the screening performance of routine urinary analysis. Decision curve analysis (DCA) was used to estimate the net benefit of routine urinary analysis. Results: A total of 927 specimens with 156 UTIs were included in the present study. The area under ROC curves (AUCs) of white blood cells (WBCs) and bacteria were 0.729 and 0.836, respectively. The logistic regression model incorporating WBCs, bacteria and nitrite together had an AUC of 0.851, which is significantly higher than that of WBCs. NRI and IDI analyses also indicated that WBCs, bacteria and nitrite, when used together, had better a screening performance than each single test alone. DCA revealed that 0.08 net benefit can be obtained for bacteria and the model, while the net benefit of WBCs is limited. Conclusions: WBCs, bacteria and nitrite, when used together, can significantly improve the efficiency for UTI screening. Bacteria and the model incorporating WBCs, bacteria and nitrite have a net benefit in UTI screening, while the net benefit of WBCs, when used alone, is limited.

Human endo

As one of the most promising solutions for the next generation Web-scale datacenter networks, hybrid software-defined networks (SDN) have received extensive attention and in-depth research in recent years. Specifically, the issues of deployment optimization and fine-grained link state management in hybrid SDNs are extremely crucial for building Web-scale and energy-efficient SDN-driven datacenters. In this paper, we introduce an energy-efficient deployment optimization scheme for hybrid SDNs, in order to reduce the deployment cost and energy consumption, so that the hybrid networks can approach or even achieve the centralized control ability of pure SDN networks. In addition, we propose fine-grained link state management algorithms with energy consumption sensing ability. With the algorithms, the link state of the hybrid SDNs can be controlled in a fine-grained way, and can be managed by dynamically clearing or temporarily closing redundant links, so as to further reduce link energy consumption. We setup experiments to demonstrate the functionality effectiveness and performance gains of the proposed scheme and algorithms, and the extensive simulation results show that, the proposed solution of this paper outperforms its competitors, producing an arresting increase of energy efficiency. Specifically, under the premise of only 20% of SDN switch deployment budget, the proposed scheme in this paper can reduce the total energy consumption by about 40%.

Hypertensive subjects often exhibit exaggerated cardiovascular reactivity. An overactive orexin system underlies the pathophysiology of hypertension. We examined orexin’s roles in eating-associated cardiovascular reactivity in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Results showed eating regular chow or palatable food (sucrose agar) was accompanied by elevated arterial pressure and heart rate. In both SHRs and WKY rats, the cardiovascular responses associated with sucrose-agar consumption were greater than that with regular-chow consumption. Additionally, SHRs exhibited greater cardiovascular responses than WKY rats did to regular-chow and palatable food consumption. Central orexin 2 receptor (OX2R) blockade attenuated sucrose-agar consumption-associated cardiovascular response only in SHRs. In both SHRs and WKY rats, OX2R blockade did not affect regular-chow consumption-associated cardiovascular responses. Greater numbers of c-Fos-positive cells in the rostral ventrolateral medulla (RVLM) and of c-Fos-positive orexin neurons in the dorsomedial hypothalamus (DMH) were detected in sucrose agar-treated SHRs, compared to regular chow-treated SHRs and to sucrose agar-treated WKY rats. Central OX2R blockade reduced the number of c-Fos-positive cells in the RVLM only in sucrose agar-treated SHRs. We concluded that in SHRs, orexin neurons in the DMH might be overactive during eating palatable food and may further elicit exaggerated cardiovascular responses via an OX2R-RVLM pathway.

Big data is anticipated to have large implications in clinical pharmacy, in view of its potential in enhancing precision medicine and to avoid medication error. However, it is equally debatable since such a powerful tool may also disrupt the need of pharmacist in healthcare industry. In this article, we commented the contribution of Big Data in various aspects of clinical pharmacy including advancing pharmaceutical care service, optimising drug supplies, managing clinical trials, and strengthening pharmacovigilance. The future direction of the usage of Big Data related to clinical pharmacy will be discussed. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Orexins are important regulators of cardiovascular functions in various physiological and pathological conditions. The dorsomedial hypothalamus (DMH), an essential mediator of cardiovascular responses to stress, contains dense orexinergic innervations and receptors. We examined whether orexins can regulate cardiovascular functions through their actions in the DMH in anesthetized rats. An intra-DMH injection of orexin A (30pmol) produced elevation of arterial pressure and heart rate. Orexin A-sensitive sites were located within or immediately adjacent to the DMH and larger responses were induced at the compact part of the dorsomedial hypothalamic nucleus. Orexin A-induced responses were attenuated by intra-DMH pretreatment with an orexin receptor 1 (OX1R) antagonist, SB-334867 (15nmol) (17.7 ± 2.8 vs. 5.2 ± 1.0mmHg; 54.6 ± 10.0 vs. 22.8 ± 7.4 beats/min). Intra-DMH applied [Ala11,D-Leu15]-orexin B (300 pmol), an orexin receptor 2 (OX2R) agonist, elicited cardiovascular responses mimicking the responses of orexin A, except for a smaller pressor response (7.4 ± 1.7 vs. 16.4 ± 1.8mmHg). In a series of experiment, effects of orexin B (100pmol) and then orexin A (30pmol), were examined at a same site. Two patterns of responses were observed in 12 intra-DMH sites: (1) both orexin A and B (9 sites), and (2) only orexin A (3 sites) induced cardiovascular responses, respectively suggesting OX1R/OX2R-mediated and OX1R-predominant mechanisms. In conclusion, orexins regulated cardiovascular functions through OX1R/OX2R- or OX1R-mediated mechanisms at different locations in the DMH.