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Abstract Chemical derivatization is a powerful strategy to enhance sensitivity and selectivity of liquid chromatography-mass spectrometry for non-targeted analysis of chemicals in complex mixtures. However, it remains impossible to obtain large sets of reference spectra for chemically derived molecules (CDMs), representing a major barrier in real-world applications. Herein, we describe a deep learning approach that enables accurate prediction of electrospray ionization tandem mass spectra for CDMs (DeepCDM). DeepCDM is established by transfer learning from a generic spectrum predicting model using a small set of experimentally acquired tandem mass spectra of CDMs, which converts a generic model with low predictability for CDMs into a specialized model with high predictability. We demonstrate DeepCDM by predicting electrospray ionization tandem mass spectra of dansylated molecules. The success in establishing Dns-MS further enables the development of DnsBank, a dansylation-specialized in silico spectral library. DnsBank achieves significant increases of accurate annotation rates of dansylated molecules, facilitating discovery of new hazardous pollutants from an environmental study of leather industrial wastewater. DeepCDM is also highly versatile for other classes of CDMs. Therefore, we envision that DeepCDM will pave a way for high-throughput identification of CDMs in non-targeted analysis to dig unknowns with potential health impacts from emerging anthropogenic chemicals.

Summary: Background: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy and safety of orally administered GST-HG171 plus Ritonavir in patients with coronavirus disease 2019 (COVID-19) infected with emerging XBB and non-XBB variants. Methods: This randomised, double-blind, placebo-controlled phase 2/3 trial was conducted in 47 sites in China among adult patients with mild-to-moderate COVID-19 with symptoms onset ≤72 h. Eligible patients were randomised 1:1 to receive GST-HG171 (150 mg) plus Ritonavir (100 mg) or corresponding placebo tablets twice daily for 5 days, with stratification factors including the risk level of disease progression and vaccination status. The primary efficacy endpoint was time to sustained recovery of clinical symptoms within 28 days, defined as a score of 0 for 11 COVID-19-related target symptoms for 2 consecutive days, assessed in the modified intention-to-treat (mITT) population. This trial was registered at ClinicalTrials.gov (NCT05656443) and Chinese Clinical Trial Registry (ChiCTR2200067088). Findings: Between Dec 19, 2022, and May 4, 2023, 1525 patients were screened. Among 1246 patients who underwent randomisation, most completed basic (21.2%) or booster (74.9%) COVID-19 immunization, and most had a low risk of disease progression at baseline. 610 of 617 who received GST-HG171 plus Ritonavir and 603 of 610 who received placebo were included in the mITT population. Patients who received GST-HG171 plus Ritonavir showed shortened median time to sustained recovery of clinical symptoms compared to the placebo group (13.0 days [95.45% confidence interval 12.0–15.0] vs. 15.0 days [14.0–15.0], P = 0.031). Consistent results were observed in both SARS-CoV-2 XBB (45.7%, 481/1053 of mITT population) and non-XBB variants (54.3%, 572/1053 of mITT population) subgroups. Incidence of adverse events was similar in the GST-HG171 plus Ritonavir (320/617, 51.9%) and placebo group (298/610, 48.9%). The most common adverse events in both placebo and treatment groups were hypertriglyceridaemia (10.0% vs. 14.7%). No deaths occurred. Interpretation: Treatment with GST-HG171 plus Ritonavir has demonstrated benefits in symptom recovery and viral clearance among low-risk vaccinated adult patients with COVID-19, without apparent safety concerns. As most patients were treated within 2 days after symptom onset in our study, confirming the potential benefits of symptom recovery for patients with a longer duration between symptom onset and treatment initiation will require real-world studies. Funding: Fujian Akeylink Biotechnology Co., Ltd.

Necrophagous phorid flies are common insects found on buried corpses, and their developmental data play a crucial role in estimating the post-burial interval (PBI). This study aimed to investigate the effects of soil type and moisture content on some life cycle parameters of two forensically important insects, Megaselia scalaris (Loew, 1866) and Dohrniphora cornuta (Bigot, 1857) (Diptera: Phoridae). Larval and pupal survival, development time, and larval body length of M. scalaris and D. cornuta were observed in three different soil types (loamy sand, sandy loam A, and sandy loam B) with six moisture contents (0%, 20%, 40%, 60%, 80%, and 100%). The results indicated that soil types, soil moisture, and their interaction significantly influenced the growth and development of both species, with moisture being the most influential factor. In each soil, 20% and 40% moisture contents were more suitable for their growth and development. Both the development time and maximum larval body length were significantly different among soil types and moisture contents. The larval period of both species lasted the longest in all soils with 0% moisture content. Additionally, a regression analysis of the relationship between larval body length and development time was performed at different moisture contents in three soils. This study expanded our knowledge of the factors that influence the development of necrophagous insects and provided some reference data for applications of M. scalaris and D. cornuta in PBI estimation.

Urban public recreation space (UPRS) is an integral part of the urban public space system. With the rise of urban tourism, these areas have evolved into important spaces for leisure and entertainment, serving both residents and tourists. However, the extent to which these spaces are shared by the two groups remains unclear. This study quantified the level of UPRS equally shared by residents and tourists in Wuhan, China, using geotagged check-in data from 74 UPRS. We evaluated and compared the resident–tourist sharing degree across various types of UPRS and explored its influencing factors using multiple linear regression (MLR). The results indicated the following: (1) The sharing degree was at a moderate level and it varied significantly across different types of UPRS. (2) Characteristic streets had the highest sharing degree, followed by cultural spaces, urban parks, and tourist scenic spots. (3) The number of nearby tourist attractions, road density, and number of transport stops positively affected sharing degree. These findings suggest that the combination layout of UPRS with other tourist attractions and enhanced accessibility can effectively improve the shared usage of UPRS.

Abstract Microbial species often occur in complex communities and exhibit intricate synergistic and antagonistic interactions. To avoid predation and compete for favorable niches, bacteria have evolved specialized protein secretion systems. The type VI secretion system (T6SS) is a versatile secretion system widely distributed among Gram-negative bacteria that translocates effectors into target cells or the extracellular milieu via various physiological processes. Pseudomonas aeruginosa is an opportunistic pathogen responsible for many diseases, and it has three independent T6SSs (H1-, H2-, and H3-T6SS). In this study, we found that the H3-T6SS of highly virulent P. aeruginosa PA14 is negatively regulated by OxyR and OmpR, which are global regulatory proteins of bacterial oxidative and acid stress. In addition, we identified a H3-T6SS effector PA14_33970, which is located upstream of VgrG3. PA14_33970 interacted directly with VgrG3 and translocated into host cells. Moreover, we found that H3-T6SS and PA14_33970 play crucial roles in oxidative, acid, and osmotic stress resistance, as well as in motility and biofilm formation. PA14_33970 was identified as a new T6SS effector promoting biofilm formation and thus named TepB. Furthermore, we found that TepB contributes to the virulence of P. aeruginosa PA14 toward Caenorhabditis elegans. Overall, our study indicates that H3-T6SS and its biofilm-promoting effector TepB are regulated by OxyR and OmpR, both of which are important for adaptation of P. aeruginosa PA14 to multiple stressors, providing insights into the regulatory mechanisms and roles of T6SSs in P. aeruginosa.

Abstract Background Patients with critical limb ischemia (CLI) are at great risk of major amputation and cardiovascular events. Adipose-derived mesenchymal stem cell (ADSC) therapy is a promising therapeutic strategy for CLI, but the poor engraftment and insufficient angiogenic ability of ADSCs limit their regenerative potential. Herein, we explored the potential of human umbilical vein endothelial cells (HUVECs)-derived small extracellular vesicles (sEVs) for enhancing the therapeutic efficacy of ADSCs in CLI. Results sEVs derived from hypoxic HUVECs enhanced the resistance of ADSCs to reactive oxygen species (ROS) and further improved the proangiogenic ability of ADSCs in vitro. We found that the hypoxic environment altered the composition of sEVs from HUVECs and that hypoxia increased the level of miR-486-5p in sEVs. Compared to normoxic sEVs (nsEVs), hypoxic sEVs (hsEVs) of HUVECs significantly downregulated the phosphatase and tensin homolog (PTEN) via direct targeting of miR-486-5p, therefore activating the AKT/MTOR/HIF-1α pathway and influencing the survival and pro-angiogenesis ability of ADSCs. In a hindlimb ischemia model, we discovered that hsEVs-primed ADSCs exhibited superior cell engraftment, and resulted in better angiogenesis and tissue repair. Conclusion hsEVs could be used as a therapeutic booster to improve the curative potential of ADSCs in a limb ischemia model. This finding offers new insight for CLI treatment. Graphical Abstract

CRISPR diagnostics are routinely used for the detecting nucleic acids, but rarely for clinically important proteins. Here, by translating a CRISPR-based DNA test into an ultrasensitive assay for antibodies, the authors achieve antibody detection from serum samples at attomolar concentrations.

In this study, the effects of the immobilized bacterial mixture (IM-FN) of Arthrobacter sp. NJ-1 and Klebsiella variicola strain FH-1 using sodium alginate-CaCl2 on the degradation of atrazine were investigated. The results showed that the optimal ratio of three types of carrier materials (i.e., rice straw powder, rice husk, and wheat bran) was 1:1:1 with the highest adsorption capacity for atrazine (i.e., 3774.47 mg/kg) obtained at 30°C. On day 9, the degradation efficiency of atrazine (50 mg/L) reached 98.23% with cell concentration of 1.6 × 108 cfu/ml at pH 9 and 30°C. The Box–Behnken method was used to further optimize the culture conditions for the degradation of atrazine by the immobilized bacterial mixture. The IM-FN could be reused for 2–3 times with the degradation efficiency of atrazine maintained at 73.0% after being stored for 80 days at 25°C. The population dynamics of IM-FN was explored with the total soil DNA samples specifically analyzed by real-time PCR. In 7 days, the copy numbers of both PydC and estD genes in the IM-FN were significantly higher than those of bacterial suspensions in the soil. Compared with bacterial suspensions, the IM-FN significantly accelerated the degradation of atrazine (20 mg/kg) in soil with the half-life shortened from 19.80 to 7.96 days. The plant heights of two atrazine-sensitive crops (wheat and soybean) were increased by 14.99 and 64.74%, respectively, in the soil restored by immobilized bacterial mixture, indicating that the IM-FN significantly reduced the phytotoxicity of atrazine on the plants. Our study evidently demonstrated that the IM-FN could significantly increase the degradation of atrazine, providing a potentially effective bioremediation technique for the treatment of atrazine-polluted soil environment and providing experimental support for the wide application of immobilized microorganism technology in agriculture.

The Hooded Crane (Grus monacha) is listed as a Vulnerable species in the IUCN red list. Tidal wetland (tideland), the major habitat for wintering Hooded Cranes at East China's Chongming Dongtan, has dramatically changed in the past two decades, but there is limited knowledge about the population and habitat changes of the Hooded Cranes. This study investigated the population size and distribution of wintering Hooded Cranes at Chongming Dongtan from 2000 to 2021. We used remote sensing images combined with a vegetation classification algorithm to analyse the distribution of saltmarsh vegetation. The quadrat method was used to investigate the density and weight of the underground corms of Sea Bulrush (Scirpus mariquter), the main food on tideland for the Hooded Cranes. From 2000 to 2021, the population number of wintering Hooded Cranes at Chongming Dongtan remained stable at approximately 100. In 2000, the area of Scirpus spp. and Common Reed (Phragmites australis) accounted for approximately half of the total saltmarsh area at Chongming Dongtan, respectively. The invasive Smooth Cordgrass (Spartina alterniflora) rapidly expanded on tideland in the 2000s while the Scirpus spp. was competed out and thus significantly reduced in area. After the implementation of an ecological project to control Smooth Cordgrass and to restore Scirpus spp. in the 2010s, the area of the Smooth Cordgrass decreased considerably while the area of Scirpus spp. increased. The corms of Sea Bulrush decreased on the southeastern tideland during the study period, which might be the cause of the northward movement of the foraging Hooded Cranes on tideland. We also found Hooded Cranes foraged crops in the nearby farmland in mid-winter, causing human-bird conflicts in the recent decade. Our results found that changes in habitat and food conditions on tideland impacted wintering Hooded Cranes. Foraging in farmland with human disturbance in the recent decade might be related to insufficient food on tideland. We suggest active intervention to accelerate the restoration of Sea Bulrush on tideland and reduce human disturbance in farmland to improve the habitat quality of the wintering Hooded Crane at Chongming Dongtan.

Abstract Background Adipose-derived mesenchymal stem cells (ADSC)-based therapy is an outstanding treatment strategy for ischaemic disease. However, the therapeutic efficacy of this strategy is not ideal due to the poor paracrine function and low survival rate of ADSCs in target regions. Platelet extracellular vesicles (PEVs) are nanoparticles derived from activated platelets that can participate in communication between cells. Accumulating evidence indicates that PEVs can regulate the biological functions of several cell lines. In the present study, we aimed to investigate whether PEVs can modulate the proangiogenic potential of ADSCs in vitro and in vivo. Methods PEVs were identified using scanning electron microscope (SEM), flow cytometry (FCM) and nanoparticle tracking analysis (NTA). The CCK8 assay was performed to detect proliferation of cells. Transwell and wound healing assays were performed to verify migration capacity of cells. AnnexinV-FITC/PI apoptosis kit and live/dead assay were performed to assess ADSCs apoptosis under Cocl2-induced hypoxia condition. The underlying mechanisms by which PEVs affected ADSCs were explored using real time-PCR(RT-PCR) and Western blot. In addition, matrigel plug assays were conducted and mouse hindlimb ischaemic models were established to investigate the proangiogenic potential of PEV-treated ADSCs in vivo. Results We demonstrated that ADSC could internalize PEVs, which lead to a series of biological reactions. In vitro, dose-dependent effects of PEVs on ADSC proliferation, migration and antiapoptotic capacity were observed. Western blotting results suggested that multiple proteins such as ERK, AKT, FAK, Src and PLCγ1 kinase may contribute to these changes. Furthermore, PEVs induced upregulation of several growth factors expression in ADSCs and amplified the proliferation, migration and tube formation of HUVECs induced by ADSC conditioned medium (CM). In in vivo experiments, compared with control ADSCs, the injection of PEV-treated ADSCs resulted in more vascularization in matrigel plugs, attenuated tissue degeneration and increased blood flow and capillary density in ischaemic hindlimb tissues. Conclusion Our data demonstrated that PEVs could enhance the proangiogenic potential of ADSCs in mouse hindlimb ischaemia. The major mechanisms of this effect included the promotion of ADSC proliferation, migration, anti-apoptosis ability and paracrine secretion.

Electrochemical N2 reduction reaction (NRR) is a promising approach for NH3 production under mild conditions. Herein, the catalytic performance of 3d transition metal (TM) atoms anchored on s-triazine-based g-C3N4 (TM@g-C3N4) in NRR is systematically investigated by density functional theory (DFT) calculations. Among these TM@g-C3N4 systems, the V@g-C3N4, Cr@g-C3N4, Mn@g-C3N4, Fe@g-C3N4, and Co@g-C3N4 monolayers have lower ΔG(*NNH) values, especially the V@g-C3N4 monolayer has the lowest limiting potential of −0.60 V and the corresponding limiting-potential steps are *N2+H++e−=*NNH for both alternating and distal mechanisms. For V@g-C3N4, the transferred charge and spin moment contributed by the anchored V atom activate N2 molecule. The metal conductivity of V@g-C3N4 provides an effective guarantee for charge transfer between adsorbates and V atom during N2 reduction reaction. After N2 adsorption, the p-d orbital hybridization of *N2 and V atoms can provide or receive electrons for the intermediate products, which makes the reduction process follow acceptance-donation mechanism. The results provide an important reference to design high efficiency single atom catalysts (SACs) for N2 reduction.

BackgroundAngiogenesis plays a critical role in the growth and metastasis of breast cancer and angiogenesis inhibition has become an effective strategy for cancer therapy. Our study aimed to clarify the key candidate genes and pathways related to breast cancer angiogenesis.MethodsDifferentially expressed genes (DEGs) in the raw breast cancer (BRCA) gene dataset from the Cancer Genome Atlas (TCGA) database were identified and gene ontology analysis of the DEGs was performed. Hub genes were subsequently determined using the Gene Expression Omnibus database. The expression of the mesenchyme homeobox 2 (MEOX2) in breast cancer cells and tissues was assessed by quantification real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively. The prognostic value of the MEOX2 gene in breast cancer tissue was evaluated with the Kaplan-Meier plotter.ResultsA total of 61 angiogenesis-related DEGs were identified in the TCGA dataset, among which the gene MEOX2 was significantly down-regulated. GO functional annotation and pathway enrichment analyses showed that MEOX2 was significantly enriched in the regulation of vasculature development. The IHC results confirmed that MEOX2 expression was repressed in breast cancer tissues and the relatively low level indicated the tissue was densely vascularized. Moreover, MEOX2 expression was significantly elevated in breast cancer cells after treatment with cisplatin (DDP) and epirubicin (EPI). Finally, the Kaplan-Meier plotter confirmed that higher expression levels of MEOX2 were related to better overall survival.ConclusionOur study revealed that the angiogenesis-associated gene MEOX2 can be used as a novel biomarker for breast cancer diagnosis and clinical therapy.

The geometrical, electronic, and optical properties of the PtS2/MoTe2 heterostructure are systematically investigated based on the density functional theory (DFT) calculations. The indirect bandgap (0.93 eV) PtS2/MoTe2 heterostructure shows high dynamical and mechanical stability at room temperature. Type-II band alignment of the system facilitates the separation of photogenerated electrons and holes at the interface. Biaxial strain and external electric field (Efield) can not only induce the band alignment of the PtS2/MoTe2 heterostructure transition from type-II to type-I, but also can realize semiconductor–metal transition. The PtS2/MoTe2 heterostructure can occur redshift with a peak appearing near infrared region and its power conversion efficiency (PCE) reaches 13.60%. These properties are beneficial for application in infrared detector and solar cells. In addition, biaxial strain enhances the light adsorption intensity of the PtS2/MoTe2 heterostructure and tensile strain expands the light adsorption range. The adsorption intensity increases with the Efield increasing, implying the Efield can effectively modulate the optical properties. Our results indicate that the PtS2/MoTe2 heterostructure has a bright prospect in the application of solar cell, infrared detector, optoelectronic and nanoelectronic devices, as well as provide a useful theoretical direction for the fabrication of PtS2/MoTe2 heterostructure.

Elevational gradients strongly affect the spatial distribution and structure of soil bacterial communities. However, our understanding of the effects and determining factors is still limited, especially in the deep soil layer. Here, we investigated the diversity and composition of soil bacterial communities in different soil layers along a 1,500-m elevational gradient in the Taibai Mountain. The variables associated with climate conditions, plant communities, and soil properties were analyzed to assess their contributions to the variations in bacterial communities. Soil bacterial richness and α-diversity showed a hump-shaped trend with elevation in both surface and deep layers. In the surface layer, pH was the main factor driving the elevational pattern in bacterial diversity, while in the deep layer, pH and soil carbon (C) availability were the two main predictors. Bacterial community composition differed significantly along the elevational gradient in all soil layers. In the surface layer, Acidobacteria, Delta-proteobacteria, and Planctomycetes were significantly more abundant in the lower elevation sites than in the higher elevation sites; and Gemmatimonadetes, Chloroflexi, and Beta-proteobacteria were more abundant in the higher elevation sites. In the deep layer, AD3 was most abundant in the highest elevation site. The elevational pattern of community composition co-varied with mean annual temperature, mean annual precipitation, diversity and basal area of trees, pH, soil C availability, and soil C fractions. Statistical results showed that pH was the main driver of the elevational pattern of the bacterial community composition in the surface soil layer, while soil C fractions contributed more to the variance of the bacterial composition in the deep soil layer. These results indicated that changes in soil bacterial communities along the elevational gradient were driven by soil properties in both surface and deep soil layers, which are critical for predicting ecosystem functions under future climate change scenarios.

The density functional theory (DFT) calculations were performed to systematically study the geometrical, electronic, thermoelectric, transport and optical properties of MoSe2/BAs van der Waals heterostructures (vdWHs). The different MoSe2 and BAs stacking configurations effect hardly on the band structure. The MoSe2/BAs vdWHs possesses excellent dynamical, thermal and mechanical stability, with a direct bandgap of 1.04 eV and type-I band alignment. The Seebeck coefficient and ZT suggest the possibility of MoSe2/BAs vdWHs for thermoelectric applications. The in-plane strains and external electric field can modulate the band structure to achieve the transition from type-I to type-II band alignment, and the direct band gap feature remains preserved. Under the in-plane strains and external electric field, one can find a remarkably high optical absorption coefficient (~105 cm−1) in the visible-ultraviolet region and the red shift in the optical absorption spectrum. Its high energy conversion efficiency of 20.08% making the heterostructure extremely potential in solar energy harvesting of low-dimensional excitonic solar cells. These properties of MoSe2/BAs vdWHs show their promising applications in optoelectronic, nanoelectronic and thermoelectronic fields.

A graphene-coated nanowire (GCNW) based plasmon waveguide is proposed to achieve outstanding guiding performance in the mid-infrared band. The modal properties of the fundamental graphene plasmon mode and modal dependence on the elliptical nanowire size, thickness and width of the low-index dielectric layer, chemical potential of graphene and the operating frequency are revealed in detail by using finite element method. Results show that the low-index layer has a significant influence on modal properties, and a propagation length over 13 μm along with an extremely small normalized mode size (~10−6) could be obtained simultaneously, which is more than two orders of magnitude smaller compared with free-standing GCNW and GCNW dimers. Besides, study on crosstalk characteristics between the adjacent structures indicates the proposed waveguide exhibits very low crosstalk. Due to these excellent transmission characteristics, the proposed configuration could be used to fabricate various functional photonic devices for the future nanoscale photonic integrated circuits.

The integrated navigation system consisting of an inertial navigation system (INS) and Global Navigation Satellite System (GNSS) provides continuous high-accuracy positioning whereas the navigation accuracy during a GNSS outage inevitably degrades owing to INS error divergence. To reduce such degradation, a gated recurrent unit (GRU) and adaptive Kalman filter (AKF)-based hybrid algorithm is proposed. The GRU network, which has advantages of high accuracy and efficiency, is constructed to predict the position variations during GNSS outage. Furthermore, this paper takes the GRU-predicted error accumulation into consideration, and introduces AKF as a supplementary methodology to improve the navigation performance. The proposed hybrid algorithm is trained and tested by practical road datasets and compared with four algorithms, including the standard KF, Multi-Layer Perceptron (MLP)-aided KF, Long Short Time Memory (LSTM) aided KF, and GRU-aided KF. Periods of 180 and 120 s GNSS outage are employed to test the performance of the proposed algorithm in different time scales. The comparison result between the standard KF and neural network-aided KF indicates that the neural network is an effective methodology for bridging GNSS outages. The performance comparison between three kinds of neural networks demonstrate that both recurrent neural networks surpass the MLP in prediction position variation, and the GRU transcends the LSTM in prediction accuracy and training efficiency. Furthermore, it is concluded that the adaptive estimation theory is an effective complement to neural network-aided navigation, as the GRU-aided AKF reduced the horizontal error of GRU-aided KF by 31.71% and 16.12% after 180 and 120 s of GNSS outage, respectively.

Global changes arouse large-scale fragmentation of forests, which has a profound impact on the balance of the global carbon cycle. However, the effect and process of temperate forest fragmentation on photosynthetic carbon uptake are not clear. We used remote sensing datasets to describe the degree of forest fragmentation and clarify the relationship between fragmentation and photosynthetic carbon uptake in the temperate forests of northeastern China. The results show that forest fragmentation has high spatial heterogeneity and promotes photosynthetic carbon uptake by 14% in the cold temperate zone and 10% in the middle temperate zone. Hydrothermal conditions are the dominant influencing path, explaining 60% of the variation in the cold temperate zone and 49% of the variation in the middle temperate zone. In addition, temperature is the dominant driver of the cold temperate zone, and water is the dominant driver of the middle temperate zone. Our research calls for a deeper understanding of the carbon cycle of fragmented temperate forests, and it is necessary to consider appropriate human intervention in forest management.

Aiming at the problem of high-precision positioning of mass-pedestrians with low-cost sensors, a robust single-antenna Global Navigation Satellite System (GNSS)/Pedestrian Dead Reckoning (PDR) integration scheme is proposed with Gate Recurrent Unit (GRU)-based zero-velocity detector. Based on the foot-mounted pedestrian navigation system, the error state extended Kalman filter (EKF) framework is used to fuse GNSS position, zero-velocity state, barometer elevation, and other information. The main algorithms include improved carrier phase smoothing pseudo-range GNSS single-point positioning, GRU-based zero-velocity detection, and adaptive fusion algorithm of GNSS and PDR. Finally, the scheme was tested. The root mean square error (RMSE) of the horizontal error in the open and complex environments is lower than 1 m and 1.5 m respectively. In the indoor elevation experiment where the elevation difference of upstairs and downstairs exceeds 25 m, the elevation error is lower than 1 m. This result can provide technical reference for the accurate and continuous acquisition of public pedestrian location information.

Aiming at the GNSS receiver vulnerability in challenging urban environments and low power consumption of integrated navigation systems, an improved robust adaptive Kalman filter (IRAKF) algorithm with real-time performance and low computation complexity for single-frequency GNSS/MEMS-IMU/odometer integrated navigation module is proposed. The algorithm obtains the scale factor by the prediction residual, and uses it to adjust the artificially set covariance matrix of the observation vector under different GNSS solution states, so that the covariance matrix of the observation vector changes continuously with the complex scene. Then, the adaptive factor is calculated by the Mahalanobis distance to inflate the state prediction covariance matrix. In addition, the one-step prediction Kalman filter is introduced to reduce the computational complexity of the algorithm. The performance of the algorithm is verified by vehicle experiments in the challenging urban environments. Experiments show that the algorithm can effectively weaken the effects of abnormal model deviations and outliers in the measurements and improve the positioning accuracy of real-time integrated navigation. It can meet the requirements of low power consumption real-time vehicle navigation applications in the complex urban environment.

Positioning accuracy and power consumption are essential performance indicators of integrated navigation and positioning chips. This paper proposes a single-frequency GNSS/MEMS-IMU/odometer real-time high-precision integrated navigation algorithm with dynamic power adaptive adjustment capability in complex environments. It is implemented in a multi-sensor fusion navigation SiP (system in package) chip. The simplified INS algorithm and the simplified Kalman filter algorithm are adopted to reduce the computation load, and the strategy of adaptively adjusting the data rate and selecting the observation information for measurement update in different scenes and motion modes is combined to realize high-precision positioning and low power consumption in complex scenes. The performance of the algorithm is verified by real-time vehicle experiments in a variety of complex urban environments. The results show that the RMS statistical value of the overall positioning error in the entire road section is 0.312 m, and the overall average power consumption is 141 mW, which meets the requirements of real-time integrated navigation for high-precision positioning and low power consumption. It supports single-frequency GNSS/MEMS-IMU/odometer integrated navigation SiP chip in real-time, high-precision, low-power, and small-volume applications.

Abstract A novel liver-targeting interferon (IFN-CSP) was successfully over-expressed in our previous work. The in vitro and in vivo investigation revealed that IFN-CSP has significant anti-hepatitis B virus (HBV) effect and liver-targeting capacity. However, due to the IFN-CSP tends to form inclusion bodies in recombinant Escherichia coli (E. coli), efficient production of the soluble liver-targeting interferon is a challenge. In view of biomedical application, novel strategies for efficiently expressing liver-targeting interferon and overcoming its poor solubility are necessary and important. In the present study, a modified mu-IFN-CSP was designed base on the amino acid mutant of the native IFN-CSP. Meanwhile, the coding sequence of mu-IFN-CSP was optimized for E. coli preferred codon and the induction conditions for expression were optimized by an orthogonal test. After amino acid mutant, codon optimization and induction conditions optimization, the solubility of Mu-IFN-CSP in E. coli was up to 98.4%. The structural comparison and molecular dynamic simulation showed that the Mu-IFN-CSP formed three structure changes and were more stable than the native IFN-CSP. Tissue sections binding assays revealed that Mu-IFN-CSP was also able to specific binding to liver. In vitro anti-HBV activity assays showed that the soluble Mu-IFN-CSP has improved anti-HBV effect in HepG2.2.15 cells compared to the native IFN-CSP. The present study reports for the first time that liver-targeting interferon Mu-IFN-CSP can be expressed as soluble form, and also contributes to further support its application as liver-targeting anti-HBV medicine.

A novel dynamic average-value model (AVM) of energy storage systems (ESS) integration in power grid for long-term control is developed and validated. It is expected to greatly improve the computational speed of power system dynamics in a long-term simulation. To end this, the development of the dynamic AVM of ESS integration including ultracapacitor, DC–DC converter, and voltage source converter is elaborated upon. A new control strategy which uses digital logic circuit is proposed to keep the ultracapacitors from overcharging without significantly increasing the charging time. To validate the proposed dynamic AVM and control strategy, case studies are carried out to perform the dynamics as affected by sudden changing of charging/discharging of ESS. The accuracy of the proposed model and controller is verified by the simulation results with that obtained from the detailed model implemented in MATLAB/Simulink. Moreover, the time-step size is enlarged greatly without sacrificing the accuracy, therefore the computational speed is improved significantly.

The dynamic performance of voltage source converter-based multi-terminal high-voltage direct current (VSC-MTDC) grid for large-scale renewable energy integration is becoming a concern. This study proposes a system-level dynamic response model of wind farm (WF)-MTDC-main AC systems, and then analyses the dynamic performance based on the singular value decomposition (SVD) technique. In the modelling, an improved virtual synchronous machine control is developed, and the interaction between AC frequency and DC voltage can be readily described. Using the SVD technique, parameters of the controllers are tuned, thereby making the AC frequency and DC voltage deviations within the limitations. Some oscillation modes of the system are observed and virtual power system stabiliser is proposed to suppress the oscillations. Additionally, the oscillation can be mitigated by emulating capacitance-based inertia response. The efficiency of the proposed model and analysis is verified through the frequency-domain and time-domain results.

Salmonella typhimurium, a Gram-negative food-borne pathogen, induces impairment in intestinal mucosal barrier function frequently. The injury is related to many factors such as inflammation, oxidative stress, tight junctions and flora changes in the host intestine. Musca domestica cecropin (Mdc), a novel antimicrobial peptide containing 40 amino acids, has potential antibacterial, anti-inflammatory, and immunological functions. It remains unclear exactly whether and how Mdc reduces colonic mucosal barrier damage caused by S. typhimurium. Twenty four 6-week-old male mice were divided into four groups: normal group, control group (S. typhimurium-challenged), Mdc group, and ceftriaxone sodium group (Cs group). HE staining and transmission electron microscopy (TEM) were performed to observe the morphology of the colon tissues. Bacterial load of S. typhimurium in colon, liver and spleen were determined by bacterial plate counting. Inflammatory factors were detected by enzyme linked immunosorbent assay (ELISA). Oxidative stress levels in the colon tissues were also analyzed. Immunofluorescence analysis, RT-PCR, and Western blot were carried out to examine the levels of tight junction and inflammatory proteins. The intestinal microbiota composition was assessed via 16s rDNA sequencing. We successfully built and evaluated an S. typhimurium-infection model in mice. Morphology and microcosmic change of the colon tissues confirmed the protective qualities of Mdc. Mdc could inhibit colonic inflammation and oxidative stress. Tight junctions were improved significantly after Mdc administration. Interestingly, Mdc ameliorated intestinal flora imbalance, which may be related to the improvement of tight junction. Our results shed a new light on protective effects and mechanism of the antimicrobial peptide Mdc on colonic mucosal barrier damage caused by S. typhimurium infection. Mdc is expected to be an important candidate for S. typhimurium infection treatment.

A symmetric graphene plasmon waveguide (SGPWG) is proposed here to achieve excellent subwavelength waveguiding performance of mid-infrared waves. The modal properties of the fundamental graphene plasmon mode are investigated by use of the finite element method. Due to the naturally rounded tips, the plasmon mode in SGPWG could achieve a normalized mode field area of ~10−5 (or less) and a figure of merit over 400 by tuning the key geometric structure parameters and the chemical potential of graphene. In addition, results show that the modal performance of SGPWG seems to improve over its circular counterparts. Besides the modal properties, crosstalk analysis indicates that the proposed waveguide exhibits extremely low crosstalk, even at a separation distance of 64 nm. Due to these excellent characteristics, the proposed waveguide has promising applications in ultra-compact integrated photonic components and other intriguing nanoscale devices.

Aiming to improve the navigation accuracy during global navigation satellite system (GNSS) outages, an algorithm based on long short-term memory (LSTM) is proposed for aiding inertial navigation system (INS). The LSTM algorithm is investigated to generate the pseudo GNSS position increment substituting the GNSS signal. Almost all existing INS aiding algorithms, like the multilayer perceptron neural network (MLP), are based on modeling INS errors and INS outputs ignoring the dependence of the past vehicle dynamic information resulting in poor navigation accuracy. Whereas LSTM is a kind of dynamic neural network constructing a relationship among the present and past information. Therefore, the LSTM algorithm is adopted to attain a more stable and reliable navigation solution during a period of GNSS outages. A set of actual vehicle data was used to verify the navigation accuracy of the proposed algorithm. During 180 s GNSS outages, the test results represent that the LSTM algorithm can enhance the navigation accuracy 95% compared with pure INS algorithm, and 50% of the MLP algorithm.

MicroRNAs (miRNAs) are important regulators of pathobiological processes in various cancer. In the present study, we demonstrated that miR-93 expression was significantly up-regulated in gastric cancer tissues compared with that in matched normal mucosal tissues. High expression of miR-93 was significantly associated with lymph node metastasis and tumor-node-metastasis (TNM) stage. Functionally, ectopic expression of miR-93 promoted cell proliferation, migration, invasion, EMT phenotypes, and repressed apoptosis and G1 cell cycle arrest in vitro, and promoted tumor formation in vivo. We further identified that tissue inhibitor of metalloproteinase 2 (TIMP2) was a direct target of miR-93 by using luciferase reporter assay, qRT-PCR, and immunoblotting assay. Furthermore, knockdown of TIMP2 with specific siRNA showed similar oncogenic effects in gastric cancer cells with that transfected with miR-93 mimics. Our findings indicated that miR-93 serves as a tumor promoter in human gastric carcinogenesis by targeting TIMP2, suggesting that miR-93 might be a promising biomarker and therapeutic target for treatment of gastric cancer.

Graphene was recently proposed as a promising alternative to support surface plasmons with superior performances in the mid-infrared range. Here, we theoretically show that high-performance and low-loss transmission of graphene plasmons can be achieved by adding a silica substrate to the graphene-covered nanowire pairs. The effect of the substrate layer on mode properties has been intensively investigated by using the finite element method. Furthermore, the results show that inserting a low index material layer between the nanowire and substrate could compensate for the loss accompanied by the substrate, thus the mode properties could be adjusted to fulfill better performance. A reasonable propagation length of 15 μm and an ultra-small normalized mode area about ~10−4 could be obtained at 30 THz. The introduction of the substrate layer is crucial for practical fabrication, which provides additional freedom to tune the mode properties. The graphene-covered nanowire pairs with an extra substrate may inspire potential applications in tunable integrated nanophotonic devices.

The ability to selectively amplify the detection signals for targets over interferences is crucial when analyzing proteins in a complicated sample matrix. Here, we describe a targeted enlargement strategy that can amplify the light-scattering signal from aptamer-functionalized gold nanoparticles (Apt-AuNP) with high specificity for quantitative protein analysis. This strategy is achieved by labeling target proteins with competitively protected Apt-AuNP probes and enlarging the probes with gold enhancement. This competitive protection strategy could effectively eliminate nonspecific protein adsorptions from a sample matrix, leading to a highly specific labeling of the target protein. As a result, the subsequent amplification of the light-scattering signal by gold enhancement only occurs in the presence of the target protein. This strategy was successfully demonstrated by analyzing human α-thrombin in human serum samples in a Western blot format.

Objective: This study aimed to investigate the association of maternal first-trimester vitamin D levels and vitamin D supplementation during pregnancy with infant atopic dermatitis (AD) and to determine the effect of variables such as mode of conception on the association. Methods: This study was based on the Shanghai sub-cohort of the International Birth Cohort of China. A total of 4051 woman–infant pairs with singleton pregnancies were recruited. Vitamin D deficiency and insufficiency were defined as serum 25-hydroxyvitamin D concentrations of 25 and 50 nmol/L, respectively. AD in infants was assessed during the first six months using a standardized questionnaire based on the British Working Party criteria. Modified Poisson regression estimated the association between maternal vitamin D status and infant AD. Results: The risk of AD in infants was higher in women with deficient 25-hydroxyvitamin D levels in the first trimester (RR: 1.77, 95% CI: 1.41–2.23). This increased risk was seen in naturally conceived pregnancies, but not in those conceived using assisted reproductive technology (ART). The incidence of AD decreased in infants of mothers who took multi-vitamin (RR: 0.79, 95% CI: 0.67–1.98) and vitamin D supplements (RR: 0.51, 95% CI: 0.37–0.71) compared to those whose mothers did not take any supplements. Maternal vitamin D deficiency had varying effects on AD risk based on passive smoking exposure and breastfeeding patterns. Conclusions: Our findings highlight the importance of monitoring and supplementing vitamin D during pregnancy, especially in specific maternal populations, to reduce the risk of AD in offspring. [ABSTRACT FROM AUTHOR]

Byline: Zhang. Zhiyong, Tang. Yanan, Li. Pugang, Qiu. Weiwen, Zhong. Genlong, Xiang. Lin A 59-year-old man without cardiovascular risk factors was admitted to emergency department with acute right hemispheric syndrome. [...]