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Influenza A viruses in animal reservoirs repeatedly cross species barrier to infect humans. Once an animal-borne virus with novel antigenicity acquired the efficient human to human transmissibility, it will become epidemic in the population. Dogs are the closest animal companions to humans and canine respiratory tract expresses both SAα2,3-(avian type) and α2,6-Gal (human type) receptors. However, the role of dogs in the ecology of influenza viruses is unclear. H3N2 avian influenza viruses transmitted to dogs around 2006 and have formed stable lineages. The long-term epidemic of avian-origin H3N2 virus in canine offers the best models to investigate the effect of dogs on the evolution of influenza viruses. Here, we carried out a systematic and comparative identification of the biological characteristics of H3N2 canine influenza viruses (CIVs) isolated in the worldwide over 10 years. We found that during the adaptation of H3N2 CIVs to dogs, H3N2 CIVs became to recognize the human-like SAα2,6-Gal receptor, gradually increased HA acid stability and replication ability in human airway epithelial cells, and acquired a 100% transmission rate via respiratory droplet in ferret model, which were essential hallmarks of being adapted to humans. We also identified that the frequency of substitutions related to human adaptation has gradually increased in H3N2 CIVs, and determined four cumulative molecular changes responsible for the increased airborne transmission ability in ferrets. Our results suggested that canine may serve as an intermediate for the adaptation of avian influenza virus to human. Continuous surveillance coordinated with risk assessment for CIVs is necessary.

A variable-switching constant-sampling frequency critical soft switching model predictive control (VSCS-MPC) method is proposed in this paper to improve the dynamic behavior, efficiency and power density of the DC/DC power converters. Firstly, this paper analyzes the boundary constraints of critical soft switching that are derived with the key parameters of the interlock time and threshold current for typical SiC and GaN devices. Then, the VSCS-MPC method is proposed for synchronous DC/DC converter. Both the current source load and resistive load converters are validated with the proposed MPC method. VSCS-MPC includes two controlling parts. First is the frequency controller to maintain the critical soft switching operation by adjusting the switching frequency based on the pre-defined boundary conditions with a constant sampling frequency. A discretized frequency controller is developed to improve the stability of the system by maintaining a fixed sampling frequency. Second part is the model predictive controller to track the output voltage/current and maintain critical soft switching during dynamic periods. The explicit optimization and oversampling methods are applied in the MPC controller to meet the high frequency demand. A large current ripple ( $\triangle i_L$ $\ge$ 200 %) is introduced to achieve the critical soft switching and reduce the inductance. The switching losses are decreased by the frequency controller and the critical soft switching is maintained especially in dynamic periods due to the fast response of MPC.

Overexpression, point mutations or translocations of protein lysine methyltransferase NSD2 was occurred in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we reported our efforts to develop a series of NSD2-PWWP1 inhibitors, and further structure-based optimization resulted a potent inhibitor 38, which has the high selectivity towards NSD2-PWWP1 domain. The detailed biological evaluation revealed that compound 38 can bind to NSD2-PWWP1 and then affect the expression of genes regulated by NSD2. The current discovery will provide a useful chemical probe to the future research in understanding the specific regulation mode of NSD2 by PWWP1 recognition, and pave the way to develop potential drugs targeting NSD2 protein.

Background: Sanghuangporus sanghuang (S. sanghuang) is a large wood-decaying mushroom that is considered a traditional Chinese herbal medicine because of its high medicinal value. The fundamental bioactive substances produced mainly include flavonoids, triterpenoids, and others. The expression of some specific genes in fungi can be effectively and selectively induced by fungal elicitors. Methods: To investigate the mechanism of fungal elicitors on the metabolites of S. sanghuang, we performed the metabolic and transcriptional profiling with elicitor treatment (ET) and without elicitor treatment (WET). A correlation analysis showed significant differences in triterpenoid biosynthetic pathways in the ET and WET groups. In addition, the structural genes associated with triterpenoids and metabolites of different triterpenoids in both groups were verified using quantitative real-time polymerase chain reaction (qRT-PCR) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results: The results displayed that three triterpenoids betulinol, betulinic acid, and 2-hydroxyoleanolic acid were detected. After the excitation treatment, the level of betulinic acid reached 2.62 times that in the WET and that of 2-hydroxyoleanolic acid increased 114.67 times that in the WET. The qRT-PCR results of the expressions of the four genes related to secondary metabolic pathways, defense gene activation, and signal transduction showed significant variations between the ET and WET groups. Conclusions: the fungal elicitors have great potential to aggregate pentacyclic triterpenoid secondary metabolites in S. sanghuang.

OBJECTIVE The island sign of non-contrast computed tomography (NCCT) is a risk factor for hematoma expansion (HE) after spontaneous intracerebral hemorrhage (sICH), but has inconsistent conclusions. A meta-analysis was performed to investigate the predictive accuracy of island sign for HE. METHODS A systematic review of published literature on island sign and hematoma expansion was conducted. The pooled sensitivity, specificity and summary receiver operating characteristics curve (SROC) were generated. The publication bias was assessed by Deeks’ funnel plot asymmetry test. RESULTS Nine studies with a total of 2,939 patients were included in the present study. The pooled sensitivity and specificity of island sign for predicting hematoma expansion was 0.50 and 0.89, respectively. The area under the curve (AUC) was 0.73 in the SROC curve. There was no significant publication bias. CONCLUSION This meta-analysis suggests that island sign of non-contrast CT has a good predictive accuracy for hematoma enlargement in intracerebral hemorrhage.

A novel palladium-catalyzed Heck/[4 + 1] decarboxylative cyclization cascade of alkene-tethered aryl iodides with α-bromoacrylic acids is reported. This strategy employs α-bromoacrylic acids as a new C1 synthon to assemble diverse heteropolycycles, such as cyclopenta[de]isoquinolinediones and cyclopenta[de]indolo[2,1-a]isoquinolinones, in moderate to excellent yields. This reaction enables the construction of three C–C bonds via sequential fused palladacycle formation, C(vinyl)–Br bond activation and decarboxylation.

On one hand, the construction of two fused five-membered carbocyclic rings remains an extremely challenging topic in organic synthesis. On the other hand, transition-metal-catalyzed dienyne cycloaddition reactions have become one of the most powerful methods for the construction of diverse cyclic frameworks. Nevertheless, these methods are limited to noble transition-meal catalysis and non-radical cycloaddition modes. Here, a radical Smiles rearrangement strategy for allowing an unprecedented [3 + 2]/[3 + 2] carboannulation of dienynes with arylsulfonyl chlorides using cheap copper catalysis is described. This cascade method represents a novel cycloaddition mode for dienyne chemistry, which occurs by the sequence of addition of arylsulfonyl radical to a dienyne, a Smiles rearrangement and radical annulation to access cyclopenta[a]indene-fused quinolinones with excellent diastereoselectivity.

Memristors will be critical components in the next generation of digital technology and artificial synapses. Researchers are investigating innovative mechanistic understanding of the memristor devices based on low-cost, solution-processable, and organic materials as promising candidates. Here, we demonstrate a novel polyelectrolyte-based memristor device, which is simply prepared by spin-coating poly(acrylic acid) (PAA) and polyethylenimine (PEI) on an indium tin oxide (ITO) substrate followed by a magnetron sputtering of the ITO as the top electrode. The device has a potential to achieve excellent resistive switching (RS) performance and synapse functionality as well as greater flexibility and transmittance when compared to the oxide-based memories. An on/off resistance ratio of 50 can be maintained without degradation for up to 20 000 cycles (flat state) and over 4000 cycles (bending to a 2 mm radius 10 000 times) in the DC sweep mode. Moreover, the device performs various synaptic functions, including spike-timing-dependent plasticity, pulse pair plasticity, and short-term and long-term plasticity in the potentiation and depression processes. The counterions and two oppositely charged polyelectrolyte chains can move in and out of each other depending on the applied electrical potential (pulse), resulting in a change in the potential drop at the interface of the polyelectrolyte bilayer and its electrodes, which can be attributed to the RS mechanism and various synaptic functions. This insight may accelerate the technological deployment of the organic resistive memories.

A palladium-catalyzed chemoselective decarboxylative annulation of different aryl iodides with cyclic β-bromoacrylic acids for the construction of interesting fused and spiro polycycles is disclosed. Notably, cyclic β-bromoacrylic acids can chemoselectively act as C1 or C2 insertion units by the use of different aryl iodides. 2-Iodo

Objective: It has recently been shown that the melanoma antigen gene (MAGE) family is expressed in various tumor cell lines but silent in normal tissues, except germ cell lines. Mageb4, a member of the MAGE family, is highly expressed in the testis and homologous in humans and mice. Whole-exome sequencing studies have identified Mageb4 as a possible X-linked cause of inherited male infertility. However, the function of Mageb4 protein remains largely unknown. Methods: Using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 9 technology, we generated a Mageb4 knockout mouse model (Mageb4−/Y) to explore the role of this gene in spermatogenesis. Results: First, immunostaining of testicular cells showed that Mageb4 is localized in the cytoplasm of spermatogonia. Second, Mageb4−/Y male mice displayed significant increases in apoptosis. However, Mageb4−/Y male mice showed normal fertility, including normal sperm concentration, sperm motility, and testicular and epididymal histology. Conclusions: These findings suggest that, despite testis-exclusive expression, Mageb4 is dispensable for mouse spermatogenesis. Future research should focus on the role of this gene in apoptosis, aiming to provide clinical guidance regarding male infertility.

This paper derives a variable-frequency critical soft-switching control method for nonisolated DC/DC converters using wide-bandgap devices. The critical soft switching control technique under maximum frequency trajectory is introduced to maintain zero voltage switching over a wide range of modulation ratios according to the load variation. The concept prevents turn-on losses that are typically much larger than the turn-off losses in SiC and GaN FETs and the latter can be further reduced by adding external drain-source capacitors. We have derived the boundary conditions for critical soft switching operation. For the reduction of inductor value and volume, a maximum available switching frequency is applied to the converter within the constraints of device requirement and soft switching boundary conditions. We demonstrate experimentally that the proposed concept reduces the power losses in the wide-bandgap devices by a factor of approximately 3, enables an increase of the switching frequency by a factor of about 5, and a decrease of the main inductance by a factor of about 10. Then variable frequency critical soft switching control method is proposed with the constraints to maintain the maximum frequency within soft switching operation. Since our test bench uses off-the-shelf inductors, the inductors are subject to significant high frequency losses. Despite this, the converter efficiency increases by 1%.

The chemoselective reaction remains a tremendous but particularly fascinating challenge in organic synthesis. Herein, we report a new domino Heck/disilylation reaction of alkene-tethered 2-(2-halophenyl)-1H-indoles with hexamethyldisilane under palladium catalysis. This procedure involving the formation of one C–C bond and two C–Si bonds proceeds efficiently through two key steps of the chemoselective Heck reaction and C–H activation by overcoming undesirable C3–H bond activation on the indoles, thus generating various disilylated tetracyclic indolo[2,1-a]isoquinolines in moderate to excellent yields. Furthermore, borylated indolo[2,1-a]isoquinolines can be produced by a Heck/borylation cascade.

Non-obstructive azoospermia is one of the most common causes of male infertility, but there is still no specific treatment drug. Given that the Oct4 (Octamer-binding transcription factor 4) has an important regulatory effect on spermatogenesis, activating it can effectively promote spermatogenesis, so it is of great value to develop Oct4-targeted drug design and elucidating its mechanism of action. Here, we screened out the Oct4-targeted drug molecule NBMA (N-benzyl-4-methoxy-2-(1-(4-(trifluoromethyl)phenyl)vinyl)aniline) by computer-assisted technology, and found that it has a significant promoting effect on spermatogenesis in the established mouse azoospermia model. Subsequently, through transcriptome sequencing and enrichment analysis, real-time fluorescent quantitative PCR (qPCR) and western blot experiments revealed that NBMA promotes the differentiation of spermatogonial stem cells by activating the Oct4 pathway, thereby promoting spermatogenesis. This study proves that NBMA is a molecule with great potential to be developed as a therapeutic drug for azoospermia. It also shows that computer-assisted, chemical and biological multidisciplinary methods play a very important role in innovative drug discovery.

Artificial optoelectronic synapses have the advantages of large bandwidth, low power consumption and low crosstalk, and are considered to be the basic building blocks of neuromorphic computing. In this paper, a two-terminal optoelectronic synaptic device with ITO-MoO x -Pt structure is prepared by magnetron sputtering. The performance of resistive switching (RS) and the photo plastic properties of the device are analyzed and demonstrated. Electrical characterization tests show that the device has a resistive HRS/LRS ratio of about 90, stable endurance, and retention characteristics of more than 104 s (85 °C). The physical mechanism of the device is elucidated by a conducting filament composed of oxygen vacancies. Furthermore, the function of various synaptic neural morphologies is successfully mimicked using UV light as the stimulation source. Including short-term/long-term memory, paired-pulse facilitation, the transition from short-term to long-term memory, and ‘learning-experience’ behavior. Integrated optical sensing and electronic data storage devices have great potential for future artificial intelligence, which will facilitate the rapid development of retina-like visual sensors and low-power neuromorphic systems.

A new palladium-catalyzed tandem cyclization of various alkene-tethered aryl iodides has been presented. In this protocol, o-bromobenzoic acids are employed as coupling parters to achieve the insertion of aromatic rings by the cleavage of C(sp2)-Br and decarboxylation, thus assembling various dibenzoisoquinolinediones and dibenzoisoquinolinones. In addition, a seven-membered ring can be constructed by the use of 8-bromo-1-naphthoic acid. Notably, this approach enables regioselective product formation and features broad substrate scope.

Background Sanghuangporus sanghuang is a well-known traditional medicinal mushroom associated with mulberry. Despite the properties of this mushroom being known for many years, the regulatory mechanisms of bioactive compound biosynthesis in this medicinal mushroom are still unclear. Lysine malonylation is a posttranslational modification that has many critical functions in various aspects of cell metabolism. However, at present we do not know its role in S. sanghuang. In this study, a global investigation of the lysine malonylome in S. sanghuang was therefore carried out. Results In total, 714 malonyl modification sites were matched to 255 different proteins. The analysis indicated that malonyl modifications were involved in a wide range of cellular functions and displayed a distinct subcellular localization. Bioinformatics analysis indicated that malonylated proteins were engaged in different metabolic pathways, including glyoxylate and dicarboxylate metabolism, glycolysis/gluconeogenesis, and the tricarboxylic acid (TCA) cycle. Notably, a total of 26 enzymes related to triterpene and polysaccharide biosynthesis were found to be malonylated, indicating an indispensable role of lysine malonylation in bioactive compound biosynthesis in S. sanghuang. Conclusions These findings suggest that malonylation is associated with many metabolic pathways, particularly the metabolism of the bioactive compounds triterpene and polysaccharide. This paper represents the first comprehensive survey of malonylation in S. sanghuang and provides important data for further study on the physiological function of lysine malonylation in S. sanghuang and other medicinal mushrooms.

The continuous zoom multi configuration method is developed, and the correlative model is established, which overcomes the limitations of traditional methods, and realizes the expected system evaluation criteria，such as MTF, REA, RMS, etc..through the balance between value function, optimization algorithm and model parameterization.

Overexpression, point mutations or translocations of protein lysine methyltransferase NSD2 was occurred in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we reported our efforts to develop a series of NSD2 PWWP1 inhibitors, and further structure-based optimization resulted a potent inhibitor 38, which has the high selectivity towards NSD2 PWWP1 domain. The detailed biological evaluation revealed that compound 38 can bind to NSD2-PWWP1 and then affect the expression of genes regulated by NSD2. We believe that the current discovery will provide a useful chemical probe to the future research in understanding the specific regulation mode of NSD2 by PWWP1 recognition.

Herein α-bromoacrylic acids have been employed as C1 insertion units to achieve the palladium-catalyzed [4 + 1] annulation of 2-iodobiphenyls, which provides an efficient platform for the construction of diverse dibenzofulvenes. This protocol enables the formation of double C(aryl)-C(vinyl) bonds via a C(vinyl)-Br bond cleavage and decarboxylation. It is particularly noteworthy that the method features a broad substrate scope, and various interesting frameworks, such as bridged ring, fused (hetero)aromatic ring, and divinylbenzene, can be successfully incorporated into the products.

Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease with a median survival time of 3-5 years. Inaccurate diagnosis, limited clinical therapy and high mortality together indicate that the development of effective therapeutics for IPF is an urgent need. In recent years, it was reported that DDRs are potential targets in anti-fibrosis treatment. Based on previous work we carried out further structure modifications and led to a more selective inhibitor

Inductor design can be a process of repetitive core searching and iterative turn and airgap calculation, where every decision to be made involves a trade-off in terms of power loss, cost and power density. This paper deeply discusses the inductor design for a transformerless DC EV battery charger where inductance and operating DC bias are required to be high ( $\mathrm{500}\ \ \mu \mathrm{H}$ and 32 A). The design of the charger's filter is discussed to provide the values of the passive components and to motivate the inductor design. Two commonly used but seldom compared winding options, Litz wire and printed circuit board, are both designed and examined with respect to power loss and difficulty of the fabrication. Through tuning of the trace width and copper weight, the PCB design can provide similar performance to the Litz wire configuration, at higher cost and increased manufacturing complexity. In order to verify the text-colorblacktheoretical calculations, high-fidelity 3D finite element analysis is performed for both inductor types. After comparison, the Litz wire implementation was chosen for its reduction in power losses, cost and manufacturing complexity. The Litz wire inductor is assembled and tested on a transformerless DC charger platform with ≥ 99% efficiency at 11 kW and ≥98% efficiency at up to 22 kW.

The transformer is one of the most bulky, expensive and lowest efficiency components in a typical electric vehicle charging system. Its removal is conducive to enabling greater proliferation of charging infrastructure and the adoption of electrified vehicles. However, simply removing it can lead to common mode voltage and leakage current issues that present a safety hazard. To address this and to be compliant with international standards, a transformerless electric vehicle charging system enabled by control is proposed without need for additional components. This is achieved by connecting the three-phase filter capacitor neutral point to the DC negative, which allows the zero sequence voltage to be controlled, thereby mitigating leakage currents. Simulations show that the leakage current of the proposed transformerless charger can be made standard compliant with the topology while experiments provide validation through zero sequence voltage and active and reactive power steps. The results demonstrate that the transformer can be removed from electric vehicle chargers.

This paper focuses on the transformerless fast charging solution of plug-in electric vehicles (PEV). In a PEV system, the chargers can be classified into three levels: ac level 1 ( 19.2 kW) [1]. For the high-power level 3 fast charging system, it is not viable to place an on-board charger due to the volume and weight. We propose two topologies for off-board non-isolated DC charger to provide fast DC charging with high-power (up to 22 kW). The proposed topology includes two stages, AC/DC rectifier and DC/DC converter. According to the grid requirement, the AC/DC rectifier topologies can be divided into single-phase and three-phase applications. For the three-phase grid interface, the design of the DC charger uses the same hardware for both the grid interface and the DC/DC stage. The development and manufacturing costs are reduced due to the symmetric design of the two stages of circuit. The leakage current issue of the non-isolated system is solved based on the proposed topologies and the volume and weight are largely decreased because of the transformerless structure. The design procedures and a typical three-phase prototype are shown in this paper to verify the proposed structures.

Background Although chronic periodontitis has previously been reported to be linked with Alzheimer's disease (AD), the pathogenesis between the two is unclear. The purpose of this study is to analyze and screen the relevant and promising molecular markers between chronic periodontitis and Alzheimer's disease (AD). Methods In this paper, we analyzed three AD expression datasets and extracted differentially expressed genes (DEGs), then intersected them with chronic periodontitis genes obtained from text mining, and finally obtained integrated DEGs. We followed that by enriching the matching the matching cell signal cascade through DAVID analysis. Moreover, the MCODE of Cytoscape software was employed to uncover the protein–protein interaction (PPI) network and the matching hub gene. Finally, we verified our data using a different independent AD cohort. Results The chronic periodontitis gene set acquired from text abstracting was intersected with the previously obtained three AD groups, and 12 common genes were obtained. Functional enrichment assessment uncovered 12 cross-genes, which were mainly linked to cell morphogenesis involved in neuron differentiation, leading edge membrane, and receptor ligand activity. After PPI network creation, the ten hub genes linked to AD were retrieved, consisting of SPP1, THY1, CD44, ITGB1, HSPB3, CREB1, SST, UCHL1, CCL5 and BMP7. Finally, the function terms in the new independent dataset were used to verify the previous dataset, and we found 22 GO terms and one pathway, "ECM-receptor interaction pathways", in the overlapping functional terms. Conclusions The establishment of the above-mentioned candidate key genes, as well as the enriched signaling cascades, provides promising molecular markers for chronic periodontitis-related AD, which may help the diagnosis and treatment of AD patients in the future.

A new palladium-catalyzed domino alkyne insertion/C–H activation/decarboxylation sequence has been developed, which provides an efficient approach for synthesizing a variety of functionalized phenanthrenes in moderate to good yields. The method shows broad substrate scope and good functional group tolerance by employing readily available materials, including aryl iodides, internal alkynes, and o-bromobenzoic acids, as three-component coupling partners.

A novel palladium-catalyzed cascade cyclization of alkene-tethered aryl halides with o-bromobenzoic acids is described, which provides an efficient avenue for building various fused hexacyclic scaf...

Vanadium dioxide (VO2) nanowire structures were synthesized by chemical vapor deposition on unpolished quartz substrates. The effects of synthesis time, from 2 h to 6 h, on VO2 nanowires structure and room temperature NO2 gas sensing properties were studied. We used field emission scanning electron microscope and X-ray diffraction to characterize the morphology and crystal structure of the nanowires. The results show that networked VO2 nanowire structure was obtained at deposition time of 4 h. The structure evolution process was related to the strong interfacial interaction and continuing growth on the rough substrate surface. We explored the sensitivity of nanowires structure to 1–5 ppm NO2 gas at room temperature. The samples at deposition time of 4 h had the highest sensitivity for the networked structure. This study provides a reference for the fabrication of high performance NO2 gas sensor based on metal oxide semiconductor nanowire structures.

During 2012–2017, we collected throat swabs from dogs in China to characterize canine influenza virus (CIV) A(H3N2) isolates. A new antigenically and genetically distinct CIV H3N2 clade possessing mutations associated with mammalian adaptation emerged in 2016 and replaced previously circulating strains. This clade probably poses a risk for zoonotic infection.

A particle-in-cell Monte Carlo collision model of a discharge chamber is established to investigate the start-up process of a miniature ion thruster. We present the discharge characteristics at different stages (the initial stage, development stage, and stable stage) according to the trend of the discharge current with time. The discharge current is the sum of the sidewall current and the backplate current. During the start-up process, the sidewall current lags behind the backplate current. The variation and distribution characteristics of the discharge current over time are determined by the electron density distribution and electric potential distribution.

A novel room temperature (RT, 25 °C) NO 2 gas sensor by utilizing porous silicon (PSi)/V 2 O 5 nanopillars (VONPs) decorated with Pd nanoparticles as sensitive materials was successfully synthesized via a facile methods that reduction of a Pd solution followed by thermal annealing of V film on PSi substrate. The NO 2 -sensing analysis revealed that the PSi/VONPs-Pd showed obviously enhanced response and selectivity towards NO 2 , as compared to PSi/VONPs and Si/VONPs. The maximum response of PSi/VONPs-Pd sensor was performed at RT, therefore it has great potential to be used as a RT NO 2 gas sensor in practical. The mechanism of gas sensing and enhanced gas response of PSi/VONPs-Pd was discussed.

Background Mosquitoes host and transmit numerous arthropod-borne viruses (arboviruses) that cause disease in both humans and animals. Effective surveillance of virome profiles in mosquitoes is vital to the prevention and control of mosquito-borne diseases in northwestern China, where epidemics occur frequently. Methods Mosquitoes were collected in the Shaanxi-Gansu-Ningxia region (Shaanxi Province, Gansu Province, and Ningxia Hui Autonomous Region) of China from June to August 2019. Morphological methods were used for taxonomic identification of mosquito species. High-throughput sequencing and metagenomic analysis were used to characterize mosquito viromes. Results A total of 22,959 mosquitoes were collected, including Culex pipiens (45.7%), Culex tritaeniorhynchus (40.6%), Anopheles sinensis (8.4%), Aedes (5.2%), and Armigeres subalbatus (0.1%). In total, 3,014,183 (0.95% of clean reads) viral sequences were identified and assigned to 116 viral species (including pathogens such as Japanese encephalitis virus and Getah virus) in 31 viral families, including Flaviviridae, Togaviridae, Phasmaviridae, Phenuiviridae, and some unclassified viruses. Mosquitoes collected in July (86 species in 26 families) showed greater viral diversity than those from June and August. Culex pipiens (69 species in 25 families) and Culex tritaeniorhynchus (73 species in 24 families) carried more viral species than Anopheles sinensis (50 species in 19 families) or Aedes (38 species in 20 families) mosquitoes. Conclusion Viral diversity and abundance were affected by mosquito species and collection time. The present study elucidates the virome compositions of various mosquito species in northwestern China, improving the understanding of virus transmission dynamics for comparison with those of disease outbreaks., Author summary Most traditional viral research methods are limited to screening for a few types of viruses with low throughput. Here, we relied on metagenomic sequencing, which is a broadly non-specific screen for any virus, for monitoring of mosquito-borne viruses in the Shaanxi-Gansu-Ningxia region of China in 2019. The baseline of viral abundance and diversity in local Culex pipiens, Culex tritaeniorhynchus, Anopheles sinensis, and Aedes mosquitoes were investigated, with 116 viral species identified in 31 viral families, including Flaviviridae, Togaviridae, Phasmaviridae, Phenuiviridae, and some unclassified viruses. This study provides a baseline survey of the viromes of mosquitoes in the study area, highlighting the necessity of strengthened monitoring of mosquito-borne pathogens.

Hypoglycemia is a serious and potentially fatal complication experienced by people with insulin-dependent diabetes. The complication is usually caused by insulin overdose, skipping meals, and/or excessive physical activities. In type 1 diabetes (T1D), on top of impaired pancreatic α-cells, excessive levels of somatostatin from δ-cells further inhibit glucagon secretion to counteract overdosed insulin. Herein, we aimed to develop a microneedle (MN) patch for transdermal delivery of a peptide (PRL-2903) that antagonizes somatostatin receptor type 2 (SSTR2) in α-cells. First, we investigated the efficacy of subcutaneously administered PRL-2903 and identified the optimal dose (i.e., the minimum effective dose) and treatment scheduling (i.e., the best administration time for hypoglycemia prevention) in a T1D rat model. We then designed an MN patch using a hyaluronic acid (HA)-based polymer. The possible effect of the polymer on stabilizing the native structure of PRL-2903 was studied by molecular dynamics (MD) simulations. The results showed that the HA-based polymer could stabilize the PRL-2903 structure by restricting water molecules, promoting intra-molecular H-bonding, and constraining torsional angles of important bonds. In vivo studies with an overdose insulin challenge revealed that the PRL-2903-loaded MN patch effectively increased the plasma glucagon level, restored the counter-regulation of blood glucose concentration, and prevented hypoglycemia. The proposed MN patch is the first demonstration of a transdermal microneedle patch designed to deliver an SSTR2 antagonist for the prevention of hypoglycemia. This counter-regulatory peptide delivery system may be applied alongside with insulin delivery systems to provide a more effective and safer treatment for people with insulin-dependent diabetes.

It is very urgent to build memristive synapses and even wearable devices to simulate the basic functions of biological synapses. The linear conductance modulation is the basis of analog memristor for neuromorphic computing. By optimizing the interface engineering wherein Ta/TiO

The theory of compound zoom system and its influence and control on aberration are the basis for the design of such systems and have practical value in engineering. The principle, modeling and error analysis are analyed. Based on the system configuration of the compound zoom system, moreover, this paper advances the algorithm analysis.