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The large high-power solid lasers, such as the National Ignition Facility (NIF) of America and the Shenguang-III (SG-III) laser facility of China, can output over 2.1 MJ laser pulse for the inertial confinement fusion (ICF) experiments. Because of the enhancement of operating flux and the expansion of laser driver scale, the problem of contamination seriously influences their construction period and operation life. During irradiation by intense laser beams, the contaminants on the metallic surface of beam tubes can be transmitted to the optical surfaces and lead to damage of optical components. For the high-power solid-state laser facilities, contamination control focuses on the slab amplifiers, spatial filters, and final-optical assemblies. In this paper, an effective solution to control contaminations including the whole process of the laser driver is put forward to provide the safe operation of laser facilities, and the detailed technical methods of contamination control such as washing, cleanliness metrology, and cleanliness protecting are also introduced to reduce the probability of laser-induced damage of optics. The experimental results show that the cleanliness level of SG-III laser facility is much better to ensure that the laser facility can safely operate at high energy flux.

Abstract Background Detecting microbial life in extraterrestrial locations is a goal of space exploration because of ecological and health concerns about possible contamination of other planets with earthly organisms, and vice versa. Previously we suggested a method for life detection based on the fact that living entities require a continual input of energy accessed through coupled oxidations and reductions (an electron transport chain). We demonstrated using earthly soils that the identification of extracted components of electron transport chains is useful for remote detection of a chemical signature of life. The instrument package developed used supercritical carbon dioxide for soil extraction, followed by chromatography or electrophoresis to separate extracted compounds, with final detection by voltammetry and tandem mass-spectrometry. Results Here we used Earth-derived soils to develop a related life detection system based on direct observation of a biological redox signature. We measured the ability of soil microbial communities to reduce artificial electron acceptors. Living organisms in pure culture and those naturally found in soil were shown to reduce 2,3-dichlorophenol indophenol (DCIP) and the tetrazolium dye 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT). Uninoculated or sterilized controls did not reduce the dyes. A soil from Antarctica that was determined by chemical signature and DNA analysis to be sterile also did not reduce the dyes. Conclusion Observation of dye reduction, supplemented with extraction and identification of only a few specific signature redox-active biochemicals such as porphyrins or quinones, provides a simplified means to detect a signature of life in the soils of other planets or their moons.

This study quantitatively assesses the resilience of the urban transport system in Changchun under extreme climatic conditions, focusing on the impacts of natural disasters such as snowstorms, strong winds and extreme low temperatures on the transport system. The vulnerability, exposure, and emergency recovery capacity of the transport system in Changchun were analyzed by constructing a comprehensive assessment framework combining multi-criteria decision analysis (MCDM) and geographic information system (GIS). Based on the meteorological and traffic data of Changchun City in the past 10 years, key indicators such as traffic network density, emergency resource distribution, traffic flow, and extreme weather frequency were selected in this study. The weights were calculated by the improved hierarchical analysis method (AHP) and entropy weighting method, and finally the traffic resilience of Changchun city was quantitatively analyzed. The results show that there are significant spatial differences in the toughness of the transport system in Changchun, of which 38.6% of the areas have very low toughness and are concentrated in the urban fringe and urban-rural areas; 25.3% of the areas are at a medium level of toughness; and 5.4% of the areas show high toughness and are mainly located in the city center and important transport hubs. This study proposes transport resilience enhancement strategies for different areas of Changchun, with special recommendations for strengthening infrastructure development, optimizing traffic management and emergency response capacity in low resilience areas. The results of this study provide a scientific basis for Changchun to cope with future extreme climate challenges, and a reference framework for other cities with similar climatic conditions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Yeast shows promise as a delivery system for drugs and vaccines due to its specific targeting and immunogenic properties. The objective of this research is to create novel and effective yeast-based methods for delivering subunit vaccines. Through the modification of yeast expression plasmids and optimization of expression techniques, a new dual-expression system has been developed. We have successfully generated a S. cerevisiae vaccine strain exhibiting stable dual expression of RBD, as well as an inducible S. cerevisiae vaccine strain with dual expression of RBD. The vaccine efficacy assay in mice indicated that the dual-RBD S. cerevisiae vaccine elicited a significantly more robust humoral and mucosal immune response in comparison to the conventional S. cerevisiae vaccine expressing RBD solely on Aga2p. This study demonstrated a cost-effective dual-expression S. cerevisiae system that not only exhibits potential in combating COVID-19, but also harbors the capacity to foster vaccine development against other infectious diseases., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Aqueous proton batteries (APBs) have recently demonstrated unprecedented advantages in the fields of ultralow temperature and high-power energy applications due to kinetically favorable proton chemistry. Proton acids (e. g. H 2 SO 4 , H 3 PO 4 ) as the common proton-conducting electrolyte, however, seriously corrode electrode materials and current collectors, resulting in limited cycle life of APBs. Here we reported protonated amine as a feasible proton transport mediator and releasing source for APBs based on its dynamic chemical dissociation equilibrium. Free protons in the electrolyte are limited to a quite low level. Consequently, the optimized electrolyte with a nearly neutral pH value significantly suppresses corrosion and broadens material selection option for APBs. The CuFe-TBA electrode exhibited a long cycle performance over 40000 cycles with only ~0.0004 % attenuation rate per cycle in the optimized electrolyte. The WO 3 and VO 2 (B) electrode also displayed high cycling stability. Benefiting from enhanced electrode stability in the optimized electrolyte, the resultant CuFe-TBA/WO 3 and CuFe-TBA/VO 2 (B) full batteries display impressive long-term cycling performance with high-capacity retention. Our work presents a proton dynamic-release electrolyte for durable APBs which is highly promising for scalable energy systems., (© 2024 Wiley-VCH GmbH.)

Zeolites are crystalline microporous materials constructed by corner-sharing tetrahedra (SiO 4 and AlO 4 ), with many industrial applications as ion exchangers, adsorbents and heterogeneous catalysts 1-4 . However, the presence of micropores impedes the use of zeolites in areas dealing with bulky substrates. Introducing extrinsic mesopores, that is, intercrystal/intracrystal mesopores, in zeolites is a solution to overcome the diffusion barrier 5-8 . Still, those extrinsic mesopores are generally disordered and non-uniform; moreover, acidity and crystallinity are always, to some extent, impaired 9 . Thus, synthesizing thermally stable zeolites with intrinsic mesopores that are of uniform size and crystallographically connected with micropores, denoted here as intrinsic mesoporous zeolite, is highly desired but still not achieved. Here we report ZMQ-1 (Zeolitic Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, no. 1), an aluminosilicate zeolite with an intersecting intrinsic meso-microporous channel system delimited by 28 × 10 × 10-rings, in which the 28-ring has a free diameter of 22.76 Å × 11.83 Å, which reaches the mesopore domain. ZMQ-1 has high thermal and hydrothermal stability with tunable framework Si/Al molar ratios. ZMQ-1 is the first aluminosilicate zeolite with an intrinsic meso-microporous channel system. The Brønsted acidity of ZMQ-1 imparts high activity and unique selectivity in the catalytic cracking of heavy oil. The position of the organic structure-directing agent (OSDA) used for ZMQ-1 synthesis was determined from three-dimensional electron diffraction (3D ED) data, which shows the unique structure-directing role of the OSDA in the formation of the intrinsic meso-microporous zeolite. This provides an incentive for preparing other stable mesopore-containing zeolites., Competing Interests: Competing interests: P.L., V.V., Y.S., X.Y. and Q.L. have filed a patent on ZMQ-1 zeolite affiliated with Qingdao Institute of Bioenergy and Bioprocess Technology (China patent application no. 2023106333337; PCT application no. PCT/CN2023/106253)., (© 2024. The Author(s).)

Background: Organic phosphate flame retardants (OPFRs) and phthalate acid esters (PAEs) are common endocrine-disrupting chemicals that cause metabolic disorders. This study aimed to assess the association between joint exposure to OPFRs and PAEs during early pregnancy in women with gestational diabetes mellitus (GDM)., Methods: Seven OPFRs and five PAEs were detected in the urine of 65 GDM patients and 100 controls using gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS). The association of OPFRs and PAEs with GDM was assessed using logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models., Results: Levels of dibutyl phthalate (DBP), di-2-ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), dimethyl phthalate (DMP), tris (2-butoxyethyl) phosphate (TBEP), tributyl phosphate (TBP), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tri-ortho-cresyl phosphate (TOCP), and triphenyl phosphate (TPHP) increased in the GDM group, and the OPFRs and PAEs, except for BBP and TMCP, were associated with GDM in the logistic regression analysis. In the WQS model, the mixture of OPFRs and PAEs was significantly positively associated with GDM (OR = 3.29, 95%CI = 1.27-8.51, P = 0.014), with TDCPP having the highest WQS index weight. BKMR analysis reinforced these results, showing that the overall association of joint exposure to the OPFRs and PAEs with GDM increased at exposure levels of the 55th to 75th percentiles. Independent exposure to TDCPP (OR = 1.42, 95%CI = 1.09-1.86, P = 0.011) and TBEP (OR = 1.29, 95%CI = 1.04-1.60, P = 0.023) were associated with an increased risk of GDM., Conclusions: Environmental exposure to OPFRs and PAEs is significantly associated with GDM. These findings provide evidence for the adverse effects of exposure to OPFRs and PAEs on the health of pregnant women., (© 2024. The Author(s).)

The dissolved organic matter (DOM) with high mobility and reactivity plays a crucial role in soil. In this study, the characteristics and phytotoxicity of DOM released from the hydrochars prepared from different feedstocks (cow manure, corn stalk and Myriophyllum aquaticum) under three hydrothermal carbonization (HTC) temperatures (180, 200 and 220°C) were evaluated. The results showed that the hydrochars had high dissolved organic carbon content (20.15 to 37.65 mg/g) and its content showed a gradual reduction as HTC temperature increased. Three fluorescent components including mixed substance of fulvic acid-like and humic acid-like substances (C1, 30.92%-58.32%), UVA humic acid-like substance (C2, 25.27%-29.94%) and protein-like substance (C3, 11.74%-41.92%) were identified in hydrochar DOM by excitation emission matrix spectra coupled with parallel factor analysis. High HTC temperature increased the relative proportion of aromatic substances (C1+C2) and humification degree of hydrochar DOM from cow manure, while it presented adverse effects on the hydrochar DOM from corn stalk and Myriophyllum. aquaticum. The principal component analysis suggested that feedstock type and HTC temperature posed significant effects on the characteristics of hydrochar DOM. Additionally, seed germination test of all hydrochar DOM demonstrated that the root length was reduced by 8.88%-26.43% in contrast with control, and the germination index values were 73.57%-91.12%. These findings provided new insights into the potential environmental effects for hydrochar application in soil., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The detection of Cerebral Microbleeds (CMBs) is crucial for diagnosing cerebral small vessel disease. However, due to the small size and subtle appearance of CMBs in susceptibility-weighted imaging (SWI), manual detection is both time-consuming and labor-intensive. Meanwhile, the presence of similar-looking features in SWI images demands significant expertise from clinicians, further complicating this process. Recently, there has been a significant advancement in automated detection of CMBs using a Convolutional Neural Network (CNN) structure, aiming at enhancing diagnostic efficiency for neurologists. However, existing methods still show discrepancies when compared to the actual clinical diagnostic process. To bridge this gap, we introduce a novel multimodal detection and classification framework for CMBs' diagnosis, termed MM-UniCMBs. This framework includes a light-weight detection model and a multi-modal classification network. Specifically, we proposed a new CMBs detection network, CMBs-YOLO, designed to capture the salient features of CMBs in SWI images. Additionally, we design an innovative language-vision classification network, CMBsFormer (CF), which integrates patient textual descriptions-such as gender, age, and medical history-with image data. The MM-UniCMBs framework is designed to closely align with the diagnostic workflow of clinicians, offering greater interpretability and flexibility compared to existing methods. Extensive experimental results show that MM-UniCMBs achieves a sensitivity of 94% in CMBs' classification and can process a patient's data within 5 s.

Minks, cats, and some other species of carnivores are susceptible of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have a high risk of transmitting SARS-CoV-2 to humans. The development of animal vaccines can be an effective measure to protect animals against SARS-CoV-2 and reduce the potential risk of human infection. We previously developed a messenger ribonucleic acid (mRNA) vaccine SYS6006 that has been proven to be an efficient coronavirus disease 2019 (COVID-19) vaccine widely used in humans. Here, we further evaluated the safety and immunogenicity of SYS6006 as an animal COVID-19 vaccine candidate for SARS-CoV-2 susceptible animals or wild animals. SYS6006 was safe and immunogenic in mice and completely protected mice against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. SYS6006 was able to induce neutralizing antibodies against the SARS-CoV-2 wild-type, Delta, and Omicron BA.2 strain on day 7 after prime immunization, and two doses of immunization could enhance the neutralizing antibody responses and produce long-lasting potent antibodies for more than 8 months in minks and cats, blue foxes, and raccoon dogs, while all immunized animals had no abnormal clinical signs during immunization. These results provided here warrant further development of this safe and efficacious mRNA vaccine platform against animal COVID-19., Competing Interests: Authors CL, QL, LC, and ZLW were employed by CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huo, Wang, Li, Xiao, Wang, Ge, Zhong, Wen, Wang, Lang, Chen, Wang, Wang, Wang, He, Guan, Shuai and Bu.)

Objective: The health of oral cavity is considered as an important indicator of aging. Oral microbiota is highly associated with the oral health, while the variation of oral microbiome in elderly population and characteristic microbes associated with aging remain unclear., Subjects and Methods: In this study, 130 elderly subjects were recruited and divided into 3 groups according to their age: Stage I group (65 ≤ years < 70), Stage II group (70 ≤ years < 75), and Stage III group (75 ≤ years < 80). Their physiological indices were analyzed with using Illumina MiSeq platform and the oral microbiome was determined by high-throughput sequencing., Results: Along with aging, the level of fasting blood glucose, systolic pressure and monocytes are significantly increased. No significant difference was detected on the whole structure of the oral microbiome among groups. While using Metastats and Spearman's correlation analysis, specific bacteria were identified as potential age- or health index-related bacterial genera including Fusobacterium, Parvimonas, Porphyromonas, Aminobacter, Collinsella, Clostridium and Acinetobacter., Conclusion: Our study revealed that the composition structure of salivary microbiota in elderly population was relatively stable while specific bacteria were correlated with age and health status, which is promising to be served as health indicators of the elderly after further exploration., (© 2024. The Author(s).)

A sequence of f -phamidol-based tetradentate phosphine ligands have been developed and successfully used in iridium-catalyzed enantioselective hydrogenation of benzophenones to deliver chiral benzhydrols in almost quantitative yields and with excellent enantioselectivities (up to >99% yield and up to >99% ee). Moreover, the catalytic system shows a broad substrate scope and functional group tolerance. The synthetic utilities of this methodology have been showcased by gram-scale experiments and the formal synthesis of levocetirizine.

OPFRs are emerging environmental pollutants with reproductive and endocrine toxicity. This study aimed to examine the association between environmental exposure to OPFRs during early pregnancy and GDM. This nested case-control study was based on a birth cohort that was constructed at a maternal and child health hospital, including 74 cases of GDM among 512 pregnant women. The OPFRs, including TBP, TBEP, TCEP, TDCPP, TMCP, TOCP, and TPHP during 10-14 weeks of pregnancy were determined using GC-MS. The association between the OPFRs and GDM was assessed using WQS and BKMR models. The levels of OPFRs were significantly elevated in GDM patients (60) compared with the controls (90). The WQS analysis showed that mixtures of the OPFRs were significantly associated with GDM (OR 1.370, 95% CI 1.036-1.810, P = 0.027), and TBP, TPHP, and TMCP were the major contributors to the mixed exposure effect. In the BKMR model, individual exposure to TBP, TPHP, and TMCP, and the interaction of TMCP with TBP and TPHP were significantly associated with GDM. Environmental exposure to OPFRs is positively associated with GDM. These findings provide evidence for the adverse effects of OPFR exposure on the health of pregnant women., (© 2024. The Author(s).)

The porcine epidemic diarrhea virus (PEDV) infection inflicted substantial economic losses upon the global pig-breeding industry. This pathogen can infect all pigs and poses a particularly high fatality risk for suckling piglets. The S1 subunit of spike protein is a crucial target protein for inducing the particularly neutralizing antibodies that can intercept the virus-host interaction and neutralize virus infectivity. In the present study, the HEK293F eukaryotic expression system was successfully utilized to express and produce recombinant S1 protein. Through quantitative analysis, five monoclonal antibodies (mAbs) specifically targeting the recombinant S1 protein of PEDV were developed and subsequently evaluated using enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and flow cytometry assay (FCA). The results indicate that all five mAbs belong to the IgG1 isotype, and their half-maximal effective concentration (EC 50 ) values measured at 84.77, 7.42, 0.89, 14.64, and 7.86 pM. All these five mAbs can be utilized in ELISA, FCA, and IFA for the detection of PEDV infection. MAb 5-F9 exhibits the highest sensitivity to detect as low as 0.3125 ng/mL of recombinant PEDV-S1 protein in ELISA, while only 0.096 ng/mL of mAb 5-F9 is required to detect PEDV in FCA. The results from antigen epitope analysis indicated that mAb 8-G2 is the sole antibody capable of recognizing linear epitopes. In conclusion, this study has yielded a highly immunogenic S1 protein and five high-affinity mAbs specifically targeting the S1 protein. These findings have significant implications for early detection of PEDV infection and provide a solid foundation for further investigation into studying virus-host interactions., (© 2024. The Author(s).)

The study explores the strategic pricing and quality improvement decisions under uncertain demand in a three-layer textile and garment supply chain. According to whether the fabric manufacturer (FM) invests in quality or not and whether the garment manufacturer (GM) or garment retailer (GR) is willing to share the costs or not, five game models are constructed to investigate the impact of different members' cost sharing on the optimal decisions and profits. By conducting a theoretical and numerical analysis, we find that: (1) The GM's or GR's cost sharing plays a positive effect on the quality improvement, as for whose cost sharing performs better in improving the quality depending on the proportion of cost sharing, and the quality improvement is highest with both members share the costs simultaneously. (2) The FM receives the highest profit when both members share the costs simultaneously, however, whose cost sharing is more profitable for the FM is also related to the proportion of cost sharing; in short, the FM always benefits from the cost sharing, no matter one member does this or two members do this. (3) The GM (GR) gains the highest profit when only the GR (GM) shares the costs, and the results indicate that if one member has shared the costs, whether the other member engaging in cost sharing could benefit the former depending on their proportions. Specifically, when the GM (GR) chooses to share the costs and the proportion is relatively low, the GR(GM) joining in cost sharing is beneficial to the former; otherwise, is harmful., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Root-knot nematodes (RKNs) pose a serious threat to crop production. Flooding soil with biogas slurry, combined with soil heating before crop planting, has the potential for RKN disease suppression. However, the actual effect of this method has not been verified under field conditions. Here, we present the results of a two-year field experiment in a greenhouse demonstrating the control effect on RKN disease and plant growth using this method, as well as its influence on the soil nematode community. Four treatments were set: untreated control (CK), local control method for RKN (CC), soil flooded with 70 % biogas slurry (BS70), and soil flooded with undiluted biogas slurry (BS100). In the first year, all three RKN control treatments significantly reduced the root-knot index ( p <  0.05). In the next year, only BS70 and BS100 still presented significantly suppressed effects ( p <  0.05), and it was more obvious under BS70 with a relative control effect of 74.6 %. In the first year, BS70 and BS100 significantly inhibited the plant height of watermelon ( p <  0.05). In the next year, however, all three RKN control treatments promoted the growth of watermelon, and their stem diameter was significantly greater than that of CK. The application of biogas slurry (BS70 and BS100) significantly increased nematode richness and the Shannon index in the second year ( p  < 0.05). However, the structure index showed no significant difference among treatments (p > 0.05), indicating that biogas slurry application did not increase the soil food web complex. Principal component analysis showed that the application of biogas slurry changed the nematode community, especially under BS70, which presented a more lasting influence. The high-level input of biogas slurry also caused soil NH 4 + -N and heavy-metal and arsenic accumulation in the first year, but these soil-pollution risks disappeared in the second year., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Herein we have developed a highly practical and efficient one-step coupling protocol for the synthesis of chiral spiro diphosphine ligands, especially for the oxa -spiro diphosphine ligands O -SDP, which showed excellent reactivity and diastereoselectivity in the asymmetric hydrogenation of a key intermediate of Sacubitril. It should be noted that the one-step coupling protocol could be operated on a kilogram scale, and the resulting ruthenium catalyst of O -SDP could hydrogenate the key intermediate of Sacubitril on an industrial scale.

Mg alloy AZ31B was directly bonded to SK7 with a low alloy content, DP980 with a high Mn content, 316L with a high Cr and high Ni content by laser-gas tungsten arc welding (GTAW) and hybrid direct lap welding. The results showed that the tensile loads of AZ31B/SK7 and AZ31B/DP980 joints were 283 N/mm and 285 N/mm respectively, while the tensile load of AZ31B/316L joint was only 115 N/mm. The fracture and interface microstructures were observed using scanning electron microscopy (SEM), electron probe microanalysis (EPMA), and identified through X-ray diffractometry (XRD). For AZ31B/SK7 and AZ31B/DP980, the interface of the front reaction area and the keyhole reaction area was mainly composed of an Fe-Al phase and an Al-Mn phase. However, for AZ31B/316L, the interface of the keyhole reaction area was mainly composed of an Fe-Al phase and an Al-Mn phase, but a multi-layer composite structure consisting of the Mg 17 Al 12 compound layer and eutectic layer was formed in the front reaction area, which led to a deterioration in the joint property. The influencing mechanism of Mn, Cr and Ni elements in steel on the properties and interface structure of the laser-GTAW lap joint between the Mg alloy and the steel was systematically analyzed.

This work reports a strategy by enhancing conjugation effect and synthesizes a symmetrical and planar compound, 1,2-bis (4,5-di(1 H -tetrazol-5-yl)-2 H -1,2,3-triazol-2-yl)diazene ( NL24 ). The incorporation of azo and 1,2,3-triazole moieties manifests a synergistic effect, amplifying the conjugation effect of the azo bridge and thereby elevating the stability of NL24 ( T d : 263 °C, IS: 7 J). Notably, NL24 , possessing a structural configuration comprising four tetrazoles harboring a total of 24 nitrogen atoms, exhibits excellent detonation performances (Δ H f : 6.06 kJ g -1 , V D : 9002 m s -1 ). This strategy achieves the balance of energy and stability of polycyclic tetrazoles and provides a direction for high-performance energetic materials.

Visual Simultaneous Localization and Mapping (VSLAM) estimates the robot's pose in three-dimensional space by analyzing the depth variations of inter-frame feature points. Inter-frame feature point mismatches can lead to tracking failure, impacting the accuracy of the mobile robot's self-localization and mapping. This paper proposes a method for removing mismatches of image features in dynamic scenes in visual SLAM. First, the Grid-based Motion Statistics (GMS) method was introduced for fast coarse screening of mismatched image features. Second, an Adaptive Error Threshold RANSAC (ATRANSAC) method, determined by the internal matching rate, was proposed to improve the accuracy of removing mismatched image features in dynamic and static scenes. Third, the GMS-ATRANSAC method was tested for removing mismatched image features, and experimental results showed that GMS-ATRANSAC can remove mismatches of image features on moving objects. It achieved an average error reduction of 29.4% and 32.9% compared to RANSAC and GMS-RANSAC, with a corresponding reduction in error variance of 63.9% and 58.0%, respectively. The processing time was reduced by 78.3% and 38%, respectively. Finally, the effectiveness of inter-frame feature mismatch removal in the initialization thread of ORB-SLAM2 and the tracking thread of ORB-SLAM3 was verified for the proposed algorithm.

Transition metal catalysts with a million turnovers and excellent selectivity are rarely reported but are crucial for the industrial manufacture of optical pure pharmaceuticals, natural products, and fine chemicals. In this paper, we report an unprecedented aninoic Ir-f-phamidol catalyst for asymmetric hydrogenation of γ-amino ketones followed by stereoselective cyclization for construction of valuable chiral 2-aryl-pyrrolidine pharmacophores. The Ir-f-phamidol catalyst showed up to 1,000,000 TON and >99% ee, as well as excellent tolerance of substrates and protecting groups, providing various chiral amino alcohol intermediates. Upon optimization of the conditions, the stereoselective cyclization reaction was highly smooth and efficient (quantitative conversions, 92 to >99% ee). Finally, this solution was applied in the preparation of high-value chiral entities containing such chiral 2-aryl-pyrrolidine pharmacophores.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that is not easily detected in the early stage. Handwriting and walking have been shown to be potential indicators of cognitive decline and are often affected by AD., Objective: This study proposes an assisted screening framework for AD based on multimodal analysis of handwriting and gait and explores whether using a combination of multiple modalities can improve the accuracy of single modality classification., Methods: We recruited 90 participants (38 AD patients and 52 healthy controls). The handwriting data was collected under four handwriting tasks using dot-matrix digital pens, and the gait data was collected using an electronic trail. The two kinds of features were fused as inputs for several different machine learning models (Logistic Regression, SVM, XGBoost, Adaboost, LightGBM), and the model performance was compared., Results: The accuracy of each model ranged from 71.95% to 96.17%. Among them, the model constructed by LightGBM had the best performance, with an accuracy of 96.17%, sensitivity of 95.32%, specificity of 96.78%, PPV of 95.94%, NPV of 96.74%, and AUC of 0.991. However, the highest accuracy of a single modality was 93.53%, which was achieved by XGBoost in gait features., Conclusions: The research results show that the combination of handwriting features and gait features can achieve better classification results than a single modality. In addition, the assisted screening model proposed in this study can achieve effective classification of AD, which has development and application prospects.

Open-domain question answering (QA) tasks require a model to retrieve inference chains associated with the answer from massive documents. The core of a QA model is the information filtering ability and reasoning ability. This article proposes a semantic knowledge reasoning graph model based on the multidimensional axiomatic fuzzy set (AFS), which can generate the knowledge graph (KG) and build reasoning paths for reading comprehension tasks through unsupervised learning. Moreover, taking advantage of the interpretable AFS framework enables the proposed model to have the ability to learn and analyze the semantic relationships between candidate documents. Meanwhile, the utilization of the multidimensional AFS acquires semantic descriptions of candidate documents more concise and flexible. The similarity degree between paragraphs is calculated according to the AFS description to generate the graph. Interpretable chains of reasoning provided by the AFS knowledge graph (AFS Graph) will serve as the basis for the answer prediction. Compared with the previous methods, the AFS Graph model presented in this article improves interpretability and reasoning ability. Experimental results show that the proposed model can achieve the state-of-the-art performance on datasets of HotpotQA, SQuAD, and Natural Questions Open.

The efficient remediation of antibiotic-contaminated soil is critical for agroecosystem and human health. Using the cost-effective and feedstock-independent hydrochar with rich oxygen-containing functional groups as a soil remediation material has become a hot concern nowadays. However, the feasibility and effectiveness of hydrochar amendment in antibiotic-contaminated soil still remain unknown. Therefore, this study investigated the remediation effect and potential mechanisms of different hydrochars from cow manure (H-CM), corn stalk (H-CS) and Myriophyllum aquaticum (H-MA) at two levels (0.5% and 1.0%) in oxytetracycline (OTC)-contaminated soil using a pot experiment. Results showed that compared with CK, OTC content in the soils amended with H-CM and H-MA was decreased by 14.02-15.43% and 9.23-24.98%, respectively, whereas it was increased by 37.03-42.64% in the soils amended with H-CS. Additionally, all hydrochar amendments effectively reduced the OTC uptake in root and shoot of Chinese cabbage by 10.41-57.99% and 31.92-65.99%, respectively. The response of soil microbial community to hydrochar amendment heavily depended on feedstock type rather than hydrochar level. The soil microbial metabolism (e.g., carbohydrate metabolism, amino acid metabolism) was enhanced by hydrochar amendment. The redundancy analysis suggested that TCA cycle was positively related to the abundances of OTC-degrading bacteria (Proteobacteria, Arthrobacter and Sphingomonas) in all hydrochar-amended soils. The hydrochar amendment accelerated the soil OTC removal and reduced plant uptake in soil-Chinese cabbage system by altering soil properties, enhancing OTC-degrading bacteria and promoting microbial metabolism. These findings demonstrated that the cost-effective and sustainable hydrochar was a promising remediation material for antibiotic-contaminated soil., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Context: Molecular dynamics (MD) was carried out to simulate the friction behavior of Ni-Cr alloy coating containing pores. The mechanical properties, displacement, abrasion depth, and defect change patterns of the coating under nano-friction were studied. It was found that the stacking fault would extend to the pores, and both tangential and normal forces decreased when the grinding ball was above the pores. Meanwhile, the pores changed the extension direction of shear strain inside the coating, and stress concentrations were generated at the pores. In addition, the deformation behavior inside the coating was influenced by the processing depth, the smaller the relative height of the grinding ball and the pore, the greater the atomic deformation around the pore. The pores changed the path of atomic movement, resulting in less deformation of the coating below the pores. The presence of pores promoted the generation of surface steps and increased the amount of wear on the coating. It was also found that pores facilitated energy release and provided space for dislocation extension, and the large accumulation of dislocations led to frictional strengthening near the pores, which enhanced the properties of the material below the pores. It was found that the increase of the pore size caused the normal force decrease and the wear performance of the coating decrease, but the thermal insulation performance would be improved., Methods: In this paper, nanoscale modeling was performed in the large-scale atomic/molecular parallel simulator (LAMMPS) simulation environment. The model was visualized and analyzed in three dimensions by Open Visualization Tool (OVITO), the common neighbor analysis (CNA) method was used to obtain the atomic structure information, and the dislocation analysis (DXA) method was applied to obtain the dislocations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A series of high-nitrogen compounds, including a unique molecule 2,2'-azobis(1,5'-bitetrazole) with a branched N 10 chain and 1,5'-bitetrazolate-2 N -oxides, were synthesized successfully based on C-N-linked 1,5'-bistetrazoles using azo coupling of N -amine bonds and N -oxide introduction strategies. All compounds were characterized by NMR spectroscopy, IR spectroscopy, elemental analysis, and differential scanning calorimetry, in which the structures of five compounds were further determined by single-crystal X-ray diffraction analysis ( 2 , T-N10B , 3a , 3b , and THX ). The nitrogen contents of these five compounds range from 63.62 ( THX ) to 83.43% ( T-N10B ), which are much higher than that of CL-20 (38.34%). The heat of formation for the prepared compounds was calculated by using the Gaussian 09 program, with T-N10B having the highest value of 5.13 kJ g -1 , about 6 times higher than that of CL-20 (0.83 kJ g -1 ). The calculated detonation performances by EXPLO5 v6.05.04 show that THX has excellent detonation performance ( D = 9581 m s -1 , P = 35.93 GPa) and a remarkable specific impulse ( I sp = 284.9 s).

Obstructive sleep apnea (OSA) is a highly prevalent type of sleep-disordered breathing, which is often comorbid with affective disorders such as anxiety. A 61-year-old woman who was diagnosed with OSA affected by anxiety disorder complained of poor sleep quality at night and anxiety symptoms, and showed chest tightness, dyspnea, snoring, and apnea events during sleep. The patient initially received treatment with positive airway pressure (PAP) combined with trazodone, and subsequently switched to auto-trilevel PAP (AtPAP) combined with trazodone therapy. The initial attempt to treat the patient's disease by auto-adjusting PAP combined with trazodone failed because of central sleep apnea (CSA), which frequently occurred at night. After switching to AtPAP combined with trazodone therapy, CSA was effectively eliminated. In addition, sleep quality, hypoxia, and anxiety disorders were improved. The first report of successful therapy of AtPAP combined with trazodone for OSA complicated by anxiety disorder provides a new therapeutic strategy for this patient population.

Nowadays, global public health crises are occurring more frequently, and accurate prediction of these diseases can reduce the burden on the healthcare system. Taking COVID-19 as an example, accurate prediction of infection can assist experts in effectively allocating medical resources and diagnosing diseases. Currently, scholars worldwide use single model approaches or epidemiology models more often to predict the outbreak trend of COVID-19, resulting in poor prediction accuracy. Although a few studies have employed ensemble models, there is still room for improvement in their performance. In addition, there are only a few models that use the laboratory results of patients to predict COVID-19 infection. To address these issues, research efforts should focus on improving disease prediction performance and expanding the use of medical disease prediction models. In this paper, we propose an innovative deep learning model Whale Optimization Convolutional Neural Networks (CNN), Long-Short Term Memory (LSTM) and Artificial Neural Network (ANN) called WOCLSA which incorporates three models ANN, CNN and LSTM. The WOCLSA model utilizes the Whale Optimization Algorithm to optimize the neuron number, dropout and batch size parameters in the integrated model of ANN, CNN and LSTM, thereby finding the global optimal solution parameters. WOCLSA employs 18 patient indicators as predictors, and compares its results with three other ensemble deep learning models. All models were validated with train-test split approaches. We evaluate and compare our proposed model and other models using accuracy, F1 score, recall, AUC and precision metrics. Through many studies and tests, our results show that our prediction models can identify patients with COVID-19 infection at the AUC of 91%, 91%, and 93% respectively. Other prediction results achieve a respectable accuracy of 92.82%, 92.79%, and 91.66% respectively, f1-score of 93.41%, 92.79%, and 92.33% respectively, precision of 93.41%, 92.79%, and 92.33% respectively, recall of 93.41%, 92.79%, and 92.33% respectively. All of these exceed 91%, surpassing those of comparable models. The execution time of WOCLSA is also an advantage. Therefore, the WOCLSA ensemble model can be used to assist in verifying laboratory research results and predict and to judge various diseases in public health events., (© 2023. The Author(s).)

Pig producers have faced considerable economic losses due to porcine epidemic diarrhea virus (PEDV) infection, emphasizing the need for PEDV antibody development. The S1/S2 junction (S1S2J) cleavage site of the S protein of PEDV is one of the major determinants of coronavirus infection success. In this study, we specifically selected the S1S2J protein of PEDV-AJ1102 (a representative strain of the G2 type) as a target protein to immunize mice and generated monoclonal antibodies (mAbs) using hybridoma technology. Three mAbs with high-binding activities to the S1S2J protein and were obtained and further analyzed. To reveal the characterization of these mAbs, variable region genes of antibodies were studied by using DNA sequencing, thereby revealing differences in their CDR3 amino acid sequences. We then developed a new method to identify the isotypes of these three mAbs. Results showed that these three antibodies were of the IgM type. As for the functions of these three mAbs, indirect immunofluorescence assay confirmed their good binding ability to Vero E6 cells infected with the PEDV-SP-C strain (G1 type). Epitope analysis showed linear epitopes for all three mAbs. These antibodies were also used to detect infected cells via flow cytometry analysis. In summary, we prepared and examined three mAbs against PEDV-S1S2J. These mAbs can be employed as detection antibodies for diagnostic reagents and further developed for other applications. We also designed a novel technique for easy and cost-saving identification of isotypes of mouse mAbs. Our results lay a good foundation for the development of research on PEDV., (© 2023. The Author(s).)

Developing catalysts with both useful enantioselectivities and million turnover numbers (TONs) for asymmetric hydrogenation of ketones is attractive for industrial production of high-value bioactive chiral entities but remains a challenging. Herein, we report an ultra-efficient anionic Ir-catalyst integrated with the concept of multidentate ligation for asymmetric hydrogenation of ketones. Biocatalysis-like efficacy of up to 99% ee (enantiomeric excess), 13,425,000 TON (turnover number) and 224 s -1 TOF (turnover frequency) were documented for benchmark acetophenone. Up to 1,000,000 TON and 99% ee were achieved for challenging pyridyl alkyl ketone where at most 10,000 TONs are previously reported. The anionic Ir-catalyst showed a novel preferred ONa/MH instead of NNa/MH bifunctional mechanism. A selective industrial route to enantiopure nicotine has been established using this anionic Ir-catalyst for the key asymmetric hydrogenation step at 500 kg batch scale, providing 40 tons scale of product., (© 2023. The Author(s).)

Background and Aim: The evolution of the false lumen after the repair of acute aortic dissection has been linked to numerous adverse clinical outcomes, including increased late mortality and a higher risk of reoperation. Despite the widespread use of chronic anticoagulation in patients who have undergone repair for acute aortic dissection, the effects of this therapy on false lumen evolution and its subsequent consequences are yet to be fully understood. This meta-analysis aimed to investigate the impact of postoperative anticoagulation on patients with acute aortic dissection., Methods: In PubMed, Cochrane Libraries, Embase, and Web of Science, we performed a systematic review of nonrandomized studies, comparing outcomes with postoperative anticoagulation vs. non-anticoagulation on aortic dissection. We investigated the status of false lumen (FL), aorta-related death, aortic reintervention, and perioperative stroke in aortic dissection patients with anticoagulation and non-anticoagulation., Results: After screening 527 articles, seven non-randomized studies were selected, including a total of 2,122 patients with aortic dissection. Out of these patients, 496 received postoperative anticoagulation while 1,626 served as controls. Meta-analyses of 7 studies revealed significantly higher FL patency in Stanford type A aortic dissection (TAAD) postoperative anticoagulation with an OR of 1.82 (95% CI: 1.22 to 2.71; Z  = 2.95; I ²=0%; P  =   0.93). Moreover, there was no statistically significant difference between the two groups in aorta-related death, aortic reintervention, and perioperative stroke with an OR of 1.31 (95% CI: 0.56 to 3.04; Z  = 0.62; I ² = 0%; P  = 0.40), 0.98 (95% CI: 0.66 to 1.47; Z  = 0.09; I ² = 23%; P  = 0.26), 1.73 (95% CI: 0.48 to 6.31; Z  = 0.83; I ² = 8%; P  = 0.35), respectively., Conclusions: Postoperative anticoagulation was associated with higher FL patency in Stanford type A aortic dissection patients. However, there was no significant difference between the anticoagulation and non-anticoagulation groups in terms of aorta-related death, aortic reintervention, and perioperative stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Gong, Lang, Qin, Meng and Xiao.)

Background: T cells and natural killer (NK) cells are essential components of the immune system and are regulated by coinhibitory and costimulatory molecules in which the B7 family and CD28 family play significant roles. Previous immune checkpoint studies on B7/CD28 family members, such as PD-1, have led to remarkable success in cancer immunotherapy. However, there is still a need to find new immune checkpoint molecules. Recent studies have demonstrated that HHLA2 exerts inhibitory and stimulatory functions on the immune system by binding to different receptors on different sites. However, the pathways between HHLA2 and its two receptors on T cells and NK cells remain controversial., Aim of Review: Here, we reviewed recent studies about HHLA2 ligand interactions with KIR3DL3 and TMIGD2. We focused on elucidating the pathways between KIR3DL3/TMIGD2 and HHLA2 as well as their function in tumour progression. We also addressed the relationship between HHLA2 expression and the clinical prognosis of cancer patients., Key Scientific Concepts of Review: KIR3DL3/TMIGD2-HHLA2 may represent novel pathways within the tumour microenvironment and serve as crucial immune checkpoints for developing novel therapeutic drugs against human cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

The highly efficient Rh/ZhaoPhos-catalysed asymmetric hydrogenation of γ-butenolides and γ-hydroxybutenolides was successfully developed. This protocol provides an efficient and practical approach to the synthesis of various chiral γ-butyrolactones, which are synthetically valuable building blocks of diverse natural products and therapeutic substances, with excellent results (up to >99% conversion and 99% ee). Further follow-up transformations have been revealed to accomplish creative and efficient synthetic routes for several enantiomerically enriched drugs via this catalytic methodology., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Obstructive sleep apnea (OSA) is the most prevalent sleep disturbance that affects approximately 936 million people worldwide and leads to extensively increased incidence of cardiovascular disease, metabolic syndrome, neurological disorders, and traffic accidents. Severe OSA patients suffer a significantly higher risk of complications and worse comorbidity outcomes. Notwithstanding, with inadequate access to contact diagnosis based on polysomnography (PSG), numerous patients with severe sleep apnea have not been diagnosed, especially during the pandemic. Moreover, how the T cell immunity is impaired in OSA remains largely unknown., Methods: We primarily investigated the T cell receptor (TCR) repertoires of 50 patients with severe OSA, 23 patients with mild-to-moderate OSA, 23 patients without OSA, and 157 healthy individuals, from their peripheral blood. Firstly, we compared the clinical characteristics, blood cell counts, the ratio of neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and CD4+/CD8+T cell count between groups. Then, we compared the diversity, clonotypes, unique VJ alleles in patients with different disease severity. Furthermore, by identifying a series of disease-associated amino acid sequences, we employed a repeated hold-out machine learning strategy to explore the optimal algorithm for calculating the TCR repertoire characteristic Index (OSA-TCI). We further confirmed its relation with clinical features by linear regression analysis. Moreover, in followup of severe OSA patients who accepted adherent non-invasive ventilation, we assessed the changes of TCR repertoires, OSA-TCI, ESS, NLR, PLR, and CD4+/CD8+T after therapy., Results: We found an unexpected increase in diversity and clonotypes in the TCR repertoire of OSA patients. Furthermore, we successfully developed a novel indicator termed OSA-TCI to summarize the unique repertoire alteration, which provided 90% of sensitivity and 87% of specificity in distinguishing severe OSA. In rationalization, OSA-TCI was found correlated to AHI, BMI, hemoglobin, N1, N2 percentage of sleep, snoring, smoking and lowest oxygen saturation, but only independently related to AHI ( R  = 0.603) and smoking ( R  = 0.22). Finally, we observed OSA-TCI in the eight severe patients decreased significantly after home noninvasive ventilation for three months during follow-up, consistently in line with the TCR repertoire improvement. In contrast, NLR, PLR, and the ratio of CD4+/CD8+T cell count were found useless to diagnose and therapeutic surveillance of severe OSA., Conclusions: Our study is the first to unveil the TCR repertoire alteration in OSA, indicates possible insidious autoimmune mechanisms underlying OSA, and suggests that TCR repertoires serve as a convenient peripheral blood biomarker for OSA assessment without long-time contact and facility/instrument occupation. It may shed light on future diagnostic, immunological, pathophysiological, and prognostic research on OSA., Competing Interests: Zhixin Zhang is the founder of Chengdu ExAb Biotechnology, LTD. Xin Yang and Xueping Wen are employed by Chengdu ExAb Biotechnology LTD., (©2023 Li et al.)

Lay Abstract: Autistic children and adolescents experience high rates of co-occurring mental health conditions, including depression and suicidality, which are frequently identified by stakeholders as treatment priorities. Unfortunately, accessing community-based mental health care is often difficult for autistic youth and their families. The first obstacle families confront is finding a provider that offers mental health treatment to autistic youth within the many service systems involved in supporting the autism community. The mental health and developmental disability systems are two of the most commonly accessed, and previous work has shown there is often confusion over which of these systems is responsible for providing mental health care to autistic individuals. In this study, we conducted a telephone survey to determine the availability of outpatient mental health services for autistic youth with depressive symptoms or suicidal thoughts or behaviors in New York City across the state's mental health and developmental disability systems. Results showed that while a greater percentage of clinics in the mental health system compared with in the developmental disability system offered outpatient mental health services to autistic youth (47.1% vs 25.0%), many more did not offer care to autistic youth and there were very few options overall. Therefore, it is important that changes to policy are made to increase the availability of services and that mental health care providers' knowledge and confidence in working with autistic youth are improved.

N6-methyladenosine (m 6 A) RNA methylation and its associated RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) are involved in tumor initiation and progression. Here, we explored the biological function and clinical significance of IGF2BP1 in intrahepatic cholangiocarcinoma (iCCA). We found that IGF2BP1 expression was upregulated by H3K27 acetylation enrichment of its promoter, which positively correlated with poor clinicopathological characteristics and survival. Gain- and loss-of-function experiments showed that IGF2BP1 overexpression (knockdown) enhanced (attenuated) iCCA growth and metastasis in vitro and in vivo. Mechanistically, IGF2BP1 not only regulated the c-Myc/p16 axis to promote iCCA growth and inhibit senescence, but also activated the ZIC2/PAK4/AKT/MMP2 axis to induce tumor metastasis. More importantly, BTYNB, a recently identified IGF2BP1 inhibitor, exerted promising anti-tumor efficacy in a patient-derived xenograft (PDX) model, and IGF2BP1 conditional knockout (cKO) reduced the tumor burden. These results demonstrate the crucial role of IGF2BP1 in iCCA progression via m 6 A-dependent modification, highlighting IGF2BP1 as a potential therapeutic target in iCCA., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objectives: Alzheimer's disease (AD) has an insidious onset, the early stages are easily overlooked, and there are no reliable, rapid, and inexpensive ancillary detection methods. This study analyzes the differences in handwriting kinematic characteristics between AD patients and normal elderly people to model handwriting characteristics. The aim is to investigate whether handwriting analysis has a promising future in AD auxiliary screening or even auxiliary diagnosis and to provide a basis for developing a handwriting-based diagnostic tool., Materials and Methods: Thirty-four AD patients (15 males, 77.15 ± 1.796 years) and 45 healthy controls (20 males, 74.78 ± 2.193 years) were recruited. Participants performed four writing tasks with digital dot-matrix pens which simultaneously captured their handwriting as they wrote. The writing tasks consisted of two graphics tasks and two textual tasks. The two graphics tasks are connecting fixed dots (task 1) and copying intersecting pentagons (task 2), and the two textual tasks are dictating three words (task 3) and copying a sentence (task 4). The data were analyzed by using Student's t -test and Mann-Whitney U test to obtain statistically significant handwriting characteristics. Moreover, seven classification algorithms, such as eXtreme Gradient Boosting (XGB) and Logistic Regression (LR) were used to build classification models. Finally, the Receiver Operating Characteristic (ROC) curve, accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Area Under Curve (AUC) were used to assess whether writing scores and kinematics parameters are diagnostic., Results: Kinematic analysis showed statistically significant differences between the AD and controlled groups for most parameters ( p  < 0.05, p  < 0.01). The results found that patients with AD showed slower writing speed, tremendous writing pressure, and poorer writing stability. We built statistically significant features into a classification model, among which the model built by XGB was the most effective with a maximum accuracy of 96.55%. The handwriting characteristics also achieved good diagnostic value in the ROC analysis. Task 2 had a better classification effect than task 1. ROC curve analysis showed that the best threshold value was 0.084, accuracy = 96.30%, sensitivity = 100%, specificity = 93.41%, PPV = 92.21%, NPV = 100%, and AUC = 0.991. Task 4 had a better classification effect than task 3. ROC curve analysis showed that the best threshold value was 0.597, accuracy = 96.55%, sensitivity = 94.20%, specificity = 98.37%, PPV = 97.81%, NPV = 95.63%, and AUC = 0.994., Conclusion: This study's results prove that handwriting characteristic analysis is promising in auxiliary AD screening or AD diagnosis., Competing Interests: XT was employed by the company Cloudbutterfly Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qi, Zhang, Wei, Zhang, Wang, Lang, Zhang and Tian.)

OmicStudio focuses on speed, quality together with flexibility. Generally, OmicStudio can not only meet the users' demand of ordinary bioinformatics data analysis, statistics, and visualization, but also provides them freedom of data mining beyond developer's framework. Additionally, unlimited to developer's aesthetics, users can get more elegant graphs through customizing. Available online https://www.omicstudio.cn., Competing Interests: Qiulei Lang is the Shareholders of LC‐Bio Technology Co. The other authors are employees of LC‐Bio., (© 2023 LC‐Bio. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Axonal transport is the essential process by which neurons actively traffic a variety of cargoes between the cell soma and axon terminals. Accordingly, dysfunctional axonal transport is linked to many nervous system conditions. Therefore, being able to image and quantify this dynamic process in live neurons of animal disease models is beneficial for understanding neuropathology and testing new therapies at the preclinical level. As such, intravital approaches have been developed to assess cargo movement in the hindlimb sciatic nerves of live, anaesthetised mice. Here, we describe an adapted method for in vivo imaging of axonal transport in intact median and ulnar nerves of the rodent forelimb. Injection of a fluorescently labelled and non-toxic fragment of tetanus neurotoxin (H C T) into the mouse forepaw permits the identification of signalling endosomes in intact axons of median and ulnar nerves. Through immunofluorescent analysis of forelimb lumbrical muscles and median/ulnar nerves, we confirmed that H C T is taken up at motor nerve terminals and predominantly locates to motor axons. We then showed that the baseline trafficking of signalling endosomes is similar between the median/ulnar nerves and the sciatic nerve in adult wild-type mice. Importantly, this adapted method can be readily tailored for assessment of additional cargoes, such as mitochondria. By measuring transport in forelimb and hindlimb nerves, comparative anatomical and functional analyses can be performed in rodent disease models to aid our understanding of peripheral nerve disease pathogenesis and response to injury., Competing Interests: The authors declare that there are no competing interests associated with the manuscript., (© 2023 The Author(s).)

Nitrogen (N) transport from terrene to river water is a major source of N in estuarine water, contributing to eutrophication, harmful algal blooms and hypoxia. However, there is a lack of holistic and systematic research on N sources and transformation in the freshwater river-estuarine water continuum. In this study, multiple stable isotope signatures of nitrate (δ 15 N-NO 3 - , δ 18 O-NO 3 - ), ammonium (δ 15 N-NH 4 + ), and suspended particulate nitrogen (δ 15 N-PN) were employed to differentiate the sources and transformations of N and calculate the proportional contribution of NO 3 - sources by Bayesian model in Qiantang River (QTR)-Hangzhou Bay (HZB) during the dry season. The results showed that: (1) Evidences from isotopic signatures suggested the occurrence of N transformation instead of conservation mixing. (2) Negative correlations between the δ 15 N-NO 3 - and δ 15 N-NH 4 + , the relationships between δ 15 N-NO 3 - and NO 3 - -N concentrations, and smaller δ 18 O-NO 3 - values were found in almost all surface water, indicating that nitrification was the dominant N transformation. (3) In addition to the nitrification evidence, significant correlations between δ 15 N-PN and δ 15 N-NH 4 + revealed that assimilation and nitrification jointly affected the N transformation in the QTR's upstream, midstream and lower tributaries, which are unaffected or less affected by tides. (4) The lack of a relationship between δ 15 N-NO 3 - and δ 18 O-NO 3 - or ln(NO 3 - ) indicated that denitrification was weakened in all surface waters. (5) Qualitative identification of N pollution sources and quantitative calculation of NO 3 - -N potential sources revealed that sewage was the dominant source of N in the QTR and the HZB, while the internal nitrification was also important factor in determining N levels. This study provided evidence to further understand the sources, transport, and transformation of N in the river-estuary continuum, which deepens the understanding of the land-ocean integrated management of N contaminant., Competing Interests: Declaration of competing interest The authors declare that this article has no competing financial interests or personal relationship that could affect the work reported., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Rationale and Objectives: To predict mutations in TP53 and PIK3CA genes in breast cancer using ultrasound (US) signatures and clinicopathology., Materials and Methods: In this study, we developed and trained a model in 386 breast cancer patients to predict TP53 and PIK3CA mutations. The clinicopathological and US characteristics (including two-dimensional and color Doppler US) were investigated. Statistically significant variables were used to build predictive models, then a combined model was developed using the multivariate logistic regression analysis., Results: Univariate and multivariate analyses revealed that calcifications on US was an independent predictor of TP53 mutation (p < 0.05), whereas diameter on US and US type were independent predictors of PIK3CA mutation in breast cancer (all p < 0.05). Meanwhile, Luminal B/Human epidermal growth factor receptor two-positive (HER2+), HER2+/estrogen receptor-negative (ER-), and triple-negative breast cancer (TNBC) subtypes were strong predictors of TP53 mutation (odds ratio [OR] = 3.13, 3.18, 3.44, respectively, all p < 0.05). HER2+/ER- and TNBC subtypes were negative predictors of PIK3CA mutation (OR = 0.223, 0.241, respectively, all p < 0.05). The areas under curves (AUCs) for PIK3CA mutation in the training set increased from 0.553-0.610 to 0.741 in the multivariate model that combined US features and molecular subtype, with a sensitivity and specificity of 80.6% and 58.7%, respectively. The application of the multivariate model in the validation set achieved acceptable discrimination (AUC = 0.715). For TP53 mutation, the AUC was 0.653., Conclusion: US is a non-invasive modality to recognize the presence of TP53 and PIK3CA mutation. The models combined with US features and molecular subtype have implications for the practical application of predicting gene mutation for individual decision-making regarding treatment planning., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Aims: Pre-eclampsia (PE) is a common obstetric disease associated with oxidative stress, systemic inflammation, and angiogenic imbalance, whereas zinc (Zn) presents anti-oxidative and anti-inflammatory effects. This study is to investigate whether zinc gluconate (ZG) supplementation may ameliorate the early signs, adverse pregnancy outcomes, and pathogenic processes of PE in an animal model., Main Methods: Forty pregnant Wistar rats were randomly divided into four groups: blank control (treated with normal saline, NS), Zn control (treated with ZG and followed by NS), PE model (treated with NS and followed by nitro-L-arginine methyl ester, L-NAME), and PE intervention (treated with ZG and followed by L-NAME). ZG (5 mg/kg/day) or NS was administered by gavage from day 0 to 19 of gestation, and L-NAME (80 mg/kg/day) or NS was subcutaneously injected from day 4 to 19 of gestation. The blood pressure, urinary protein, and pregnancy outcomes were recorded. Oxidative stress, inflammation, and angiogenic homeostasis were evaluated., Key Findings: PE rats exhibited oxidative stress (reduced SOD, CAT, and GSH, and increased MDA and 3-NT), inflammation (increased IL-6 and TNF-α), and angiogenic imbalance (reduced VEGF and PlGF, and increased sFlt-1). After intervention with ZG, the blood pressure and urinary protein levels were reverted, and the pregnancy outcomes were improved. The oxidative stress, inflammation, and angiogenic imbalance were effectively restored in accompany by increased Zn and MT levels., Significance: ZG can ameliorate the early signs and pathological processes of PE in the animal model, indicating the value of zinc supplementation during pregnancy for PE prevention., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This article seeks to provide an exploration of the contributors to the mental health of Black and African Americans. We explore the foundations of racism in this country as well as factors leading to systemic racism. It is important to gain an understanding of the multifaceted contributors to disparities in health care and mental health care. Black children and adolescents experience more poverty, discrimination, marginalization, and racism compared with their white counterparts in the United States (APA, 2017). These are factors that greatly impact the mental health of this population. In addition to exploring examples of disparities in diagnosis, treatment, and research on Black youth, we also provide recommendations for clinicians seeking to provide exemplary culturally sensitive care that recognizes the diverse and multifaceted nature of this population., Competing Interests: Disclosure Q. Lang reports no financial relationships or interests. T. Roberson-Moore reports no financial relationships or interests. K.M. Rogers reports no financial relationships or interests. W.E. Wilson reports no financial relationships or interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The coronavirus disease 2019 pandemic has caused more than 532 million infections and 6.3 million deaths to date. The reactive and neutralizing fully human antibodies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective detection tools and therapeutic measures. During SARS-CoV-2 infection, a large number of SARS-CoV-2 reactive and neutralizing antibodies will be produced. Most SARS-CoV-2 reactive and neutralizing fully human antibodies are isolated from human and frequently encoded by convergent heavy-chain variable genes. However, SARS-CoV-2 viruses can mutate rapidly during replication and the resistant variants of neutralizing antibodies easily survive and evade the immune response, especially in the face of such focused antibody responses in humans. Therefore, additional tools are needed to develop different kinds of fully human antibodies to compensate for current deficiency. In this study, we utilized antibody humanized CAMouse HG mice to develop a rapid antibody discovery method and examine the antibody repertoire of SARS-CoV-2 RBD-reactive hybridoma cells derived from CAMouse HG mice by using high-throughput single-cell V(D)J sequencing analysis. CAMouse HG mice were immunized by 28-day rapid immunization method. After electrofusion and semi-solid medium screening on day 12 post-electrofusion, 171 hybridoma clones were generated based on the results of SARS-CoV-2 RBD binding activity assay. A rather obvious preferential usage of IGHV6-1 family was found in these hybridoma clones derived from CAMouse HG mice, which was significantly different from the antibodies found in patients with COVID-19. After further virus neutralization screening and antibody competition assays, we generated a noncompeting two-antibody cocktail, which showed a potent prophylactic protective efficacy against SARS-CoV-2 in cynomolgus macaques. These results indicate that humanized CAMouse HG mice not only provide a valuable platform to obtain fully human reactive and neutralizing antibodies but also have a different antibody repertoire from humans. Thus, humanized CAMouse HG mice can be used as a good complementary tool in discovery of fully human therapeutic and diagnostic antibodies., Competing Interests: Author MW is part-time employed by Chongqing Jinmaibo Bio. MW, LG and XL are shareholders of Chongqing Jinmaibo Bio. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Chi, Wu, Wang, Lang, Han, Wang, Liu, Li, Wang, Huang, Bi, Liang, Gao, Zhao, Feng, Yang, Wang, Xia and Ge.)

The gut microbiota and metabolites play pivotal roles in the pathobiology of various diseases. Here, we describe a protocol to profile the gut microbiome and meta-metabolome of a mouse disease model for acute graft-versus-host disease. We describe steps for fecal sample collection and processing for 16S sequencing and UPLC-MS. Finally, we detail the steps for data analysis and exhibit multi-omic associations to correlate with pathology. For complete details on the use and execution of this protocol, please refer to Li et al. (2020)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Gallbladder cancer (GBC) is a mortal malignancy with limited therapeutic strategies. We aimed to develop novel immune scoring systems focusing on B7-H3, B7-H4, and HHLA2. We further investigated their potential clinical effects in predicting survival and immunotherapeutic efficacy for GBC., Methods: This was a retrospective cohort study in a single center that explored the expression characteristics of B7-H3, B7-H4, and HHLA2. The immune scoring nomograms for prognostic were developed via logistic regression analyses. Their performance was evaluated using the Harrell concordance index (C-index) and decision curves analysis (DCA), and validated with calibration curves., Results: B7-H3, B7-H4, and HHLA2 manifested with a relatively high rate of co-expression patterns in GBC tissues. They were associated with worse clinicopathological stage, suppression of immune microenvironment, and unfavorable prognosis in postoperative survival. B7 stratification established based on B7-H3, B7-H4, and HHLA2 was an independent prognostic predictor (p<0.05 in both groups). Moreover, immune stratification was also successfully constructed based on B7 stratification and the density of CD8 + TILs (all p<0.001). The prediction models were developed based on B7-/or immune stratification combined with the TNM/or Nevin staging system. These novel models have excellent discrimination ability in predicting survival and immunotherapeutic efficacy for GBC patients by DCA and clinical impact plots. Finally, dynamic nomograms were developed for the most promising clinical prediction models (B7-TNM model and Immune-TNM model) to facilitate prediction., Conclusions: Immune scoring systems focusing on B7-H3, B7-H4, and HHLA2 may effectively stratify the prognosis of GBC. Prognostic nomograms based on novel immune scoring systems may potentially predict survival and immunotherapeutic efficacy in GBC. Further valid verification is necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lv, Han, Wu, Liang, Li, Zhang, Lang, Zhong, Fu, Yu, Xu and Tian.)

All-nitrogen materials, as a unique branch of energetic materials, have gained huge attentions, of which cyclo-N 5 - derivatives are the representative synthetically reported materials. However, the energetic performance of cyclo-N 5 - compounds has certain limitations and cannot go beyond that of CL-20. In order to reach the higher energy, in this work, we presented two kinds of polynitrogen species, N 4 and N 8 . Two isomers of N 4 and four isomers of N 8 were fully calculated by using density functional theory (DFT). Theoretical results show that all these polynitrogen materials exhibit excellent heats of formation (7.92-16.60 kJ g -1 ), desirable detonation performance (D: 9766-11620 m s -1 ; p : 36.8-61.1 GPa), as well as the remarkable specific impulses (330.1-436.2 s), which are much superior to CL-20. Among them, N 4 -2 (tetraazahedrane) (D: 10037 m s -1 ; p : 40.1 GPa; I sp : 409.7 s) and cube N 8 -4 (D: 11620 m s -1 ; p : 61.1 GPa; I sp : 436.2 s) have the highest energetic properties, which are expected to become promising high-energy-density-materials. Moreover, electrostatic surface potentials, Frontier molecular orbitals, infrared spectra, natural bond orbital charges, and weak interactions were also investigated to further understand their relationship between structure and performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lang, Lin, Wang, Xu and Lu.)

Advanced gallbladder cancer (GBC) is one of the most malignant of all types of biliary tract cancers that is associated with poor prognosis and high mortality. Accumulating evidence suggest that the B7 family of proteins serve an essential role in various types of cancers, including GBC. However, the potential function and regulatory mechanism of human endogenous retrovirus‑H long terminal repeat‑associating protein 2 (HHLA2; also known as B7‑H7 or B7H5) in GBC remain poorly understood. In the present study, immunohistochemistry was used to examine the expression pattern of HHLA2 in samples from 89 patients with GBC. The possible association between HHLA2 expression and the clinicopathological parameters, including prognosis, were then assessed. Using lentiviruses, overexpression of HHLA2 plasmid or short‑hairpin RNA (shRNA) of HHLA2 were transfected into GBC‑SD cells to overexpress or knock down HHLA2 expression, respectively. The effects of HHLA2 overexpression and knockdown on the epithelial‑mesenchymal transition (EMT) process on GBC‑SD cells were measured by the western blotting and immunofluorescence staining of collagen I, N‑cadherin, E‑cadherin, vimentin and α‑SMA. By contrast, changes in cell proliferation were measured using EdU assay. Cell invasion and migration were assessed using Transwell and wound‑healing assays, respectively. In addition, a xenograft mouse model was established to evaluate the tumorigenic ability of the GBC cell line in vivo after stable transfection with lentivirus for HHLA2 overexpression or shRNA for HHLA2 knockdown. The regulatory relationships among TGF‑β1, long non‑coding RNA (lncRNA) H19 (H19) and HHLA2 were then investigated. The mRNA expression of lncRNA H19 were assessed using reverse transcription‑quantitative PCR, whereas the expression levels of HHLA2 were detected by western blotting and immunofluorescence staining. HHLA2 expression was found to gradually increase as the stages of the GBC samples become more advanced. In addition, the expression level of HHLA2 was calculated to be positively associated with the Nevin stage, American Joint Committee on Cancer stage, tumor invasion and regional lymph node metastasis but was negatively associated with the overall patient survival (OS). In vitro experiments demonstrated that overexpression of HHLA2 promoted GBC migration, invasion, proliferation and EMT, whereas in vivo experiments found a promoting role of HHLA2 overexpression on GBC tumor growth. After transfection with lentiviruses encoding the overexpression plasmid of lncRNA H19, GBC migration, invasion, proliferation and EMT were increased. By contrast, knocking down HHLA2 expression suppressed TGF‑β1‑ or lncRNA H19 overexpression‑induced GBC migration, invasion, proliferation and EMT. In addition, HHLA2 knockdown significantly reduced the sizes of the GBC tumors in vivo . These results suggest that HHLA2 overexpression can promote GBC progression. Conversely, ablation of HHLA2 expression inhibited both TGF‑β1‑ and lncRNA H19‑induced GBC progression, suggesting that HHLA2 is a potential therapeutic target for this disease.