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Abstract Laboratory automation technologies have revolutionized biomedical research. However, the availability of automation solutions at the single-cell level remains scarce, primarily owing to the inherent challenges of handling cells with such small dimensions in a precise, biocompatible manner. Here, we present a single-cell-level laboratory automation solution that configures various experiments onto standardized, microscale test-tube matrices via our precise ultrasonic liquid sample ejection technology, known as PULSE. PULSE enables the transformation of titer plates into microdroplet arrays by printing nanodrops and single cells acoustically in a programmable, scalable, and biocompatible manner. Unlike pipetting robots, PULSE enables researchers to conduct biological experiments using single cells as anchoring points (e.g., 1 cell vs. 1000 cells per “tube”), achieving higher resolution and potentially more relevant data for modeling and downstream analyses. We demonstrate the ability of PULSE to perform biofabrication, precision gating, and deterministic array barcoding via preallocated droplet-addressable primers. Single cells can be gently printed at a speed range of 5–20 cell⋅s−1 with an accuracy of 90.5–97.7%, which can then adhere to the substrate and grow for up to 72 h while preserving cell integrity. In the deterministic barcoding experiment, 95.6% barcoding accuracy and 2.7% barcode hopping were observed by comparing the phenotypic data with known genotypic data from two types of single cells. Our PULSE platform allows for precise and dynamic analyses by automating experiments at the single-cell level, offering researchers a powerful tool in biomedical research.

Abstract There is a growing interest in the creation of engineered condensates formed via liquid–liquid phase separation (LLPS) to exert precise cellular control in prokaryotes. However, de novo design of cellular condensates to control metabolic flux or protein translation remains a challenge. Here, we present a synthetic condensate platform, generated through the incorporation of artificial, disordered proteins to realize specific functions in Bacillus subtilis. To achieve this, the “stacking blocks” strategy is developed to rationally design a series of LLPS-promoting proteins for programming condensates. Through the targeted recruitment of biomolecules, our investigation demonstrates that cellular condensates effectively sequester biosynthetic pathways. We successfully harness this capability to enhance the biosynthesis of 2’-fucosyllactose by 123.3%. Furthermore, we find that condensates can enhance the translation specificity of tailored enzyme fourfold, and can increase N-acetylmannosamine titer by 75.0%. Collectively, these results lay the foundation for the design of engineered condensates endowed with multifunctional capacities.

Abstract Background Epstein-Barr virus (EBV) can be reactivated and proliferated with fatal outcome in immuno-compromised people, but the clinical consequences of EBV infection in patients with severe fever with thrombocytopenia syndrome (SFTS) remain uncertain. In this study, we investigated the infection rate, the influence and the early predictors of EBV infection in SFTS patients. Methods In this retrospective study, SFTS patients who were treated in the First Affiliated Hospital of Nanjing Medical University from May 2011 to August 2021 were enrolled and divided into infected and non-infected groups. We compared the demographic characteristics, clinical manifestations and signs, laboratory tests and prognosis, and explored the risk factors of EBV infection by receiver operating characteristic (ROC) curve and logistic regression. Results A total of 120 hospitalized SFTS patients with EBV-DNA testing were enrolled in this study. Patients with EBV infection had statistically significant higher mortality rate (32.0% vs. 11.43%, P = 0.005). Compared with the non-infected group, the EBV-infected group had higher levels of C-reactive protein (CRP), creatine-kinase (CK), fasting blood glucose (FBG), blood urea nitrogen (BUN), D-dimer, and CD56+ cell counts, lower levels of immunoglobulin G (IgG), IgM, complement 3 (C3), and C4. The proportion of patients with age ≥ 60 years and ferritin > 1500.0 ng/ml in the EBV-infected group was significantly higher than that in the non-infected group. The results of ROC analysis showed that the cut-off values of CRP, IgG, C3, C4, and CD56+ cell counts to predict EBV infection were 13.2 mg/l, 12.5 g/l, 1.1 g/l, 0.6 g/l, 0.3 g/l, and 94.0 cells/µl. Multivariable logistic analysis showed that age ≥ 60 years old, CRP > 13.2 mg/l, BUN > 5.4 mmol/l, ferritin > 1500.0 ng/ml, IgG 94.0 cells/µl were the independent risk factors of EBV infection in SFTS patients. Conclusions SFTS combined with EBV infection is associated with high morbidity and mortality. It is necessary to strengthen screening for EBV infection and its early predictive markers after admission in SFTS patients.

Abstract Previous observational inquiries have revealed a correlation between depression and infectious maladies. This study seeks to elucidate the causal linkages between depression, specifically Major Depressive Disorder (MDD), and infectious diseases. Nevertheless, the causative nature of the association between MDD and infectious diseases remains elusive. Two-sample Mendelian Randomization (MR) analyses was executed utilizing single nucleotide polymorphisms (SNPs) significantly connected with MDD and infectious diseases as instrumental variables (IVs). A series of sensitivity analyses were subsequently conducted. Genetic variants linked to MDD were employed as instrumental variables sourced from a genome-wide meta-analyses comprising 500,199 individuals. Summary-level data on five infectious diseases, including candidiasis, pneumonia, skin and soft tissue infections (SSTI), upper respiratory tract infections (URTI), and urinary tract infections (UTI), were acquired from the UK Biobank and FinnGen study. Our findings evinced that genetically predicted MDD exhibited a heightened risk of candidiasis (OR = 1.52, 95% CI 1.06–2.17; P = 2.38E-02), pneumonia (OR = 1.14, 95% CI 1.01–1.29; P = 3.16E-02), URTI (OR = 1.23, 95% CI 1.12–1.36; P = 3.71E-05), and UTI (OR = 1.26, 95% CI 1.12–1.42; P = 8.90E-05). Additionally, we identified bidirectional causal relationships between UTI and MDD. The associations between MDD and the risk of URTI and UTI remained consistent in multivariable MR analyses, accounting for genetically predicted smoking and body mass index. In conclusion, this investigation ascertained a causal connection between MDD and the susceptibility to infectious diseases, particularly URTI and UTI.

IntroductionThyroid-associated ophthalmopathy (TAO) is considered to be an organ-specific autoimmune disease. Polymorphonuclear neutrophils (PMN) have been implicated in the pathogenesis of TAO. However, little is known about the role of PMN in the development of TAO, much less the relationship between PMN with B cells and CD4+T cells in TAO.ObjectiveThis study aims to investigate the phenotypic characteristics of PMN and the relationship between PMN with CD4+T cell and B cell subsets in the pathogenesis of TAO.MethodsBlood routine information was collected from 135 TAO patients, 95 Grave’s disease without TAO (GD) patients, and 116 normal controls (NC), while surface marker expression of PMN and the level of CD4+T cell and B cell subsets in peripheral blood from 40 TAO patients, 17 GD patients, and 45 NC was assessed by flow cytometry.ResultThe level of PMN, CD62L+PMN, CD54+PMN, CD4+T cells, and Th17 cells displayed an increase in TAO patients than NC, while Treg cells were lower in the TAO group compared to NC. There was no statistical difference in Th1 and plasma cells among the groups. PMN were positively correlated with Th17 cells, but not the Th1, Treg, and plasma cells.ConclusionIn the present study, we found that the percentage of PMN and PMN subset cells was significantly higher in TAO than in NC, and PMN were positively correlated with Th17 cells. It suggests that PMN may be involved in the immunopathogenesis of TAO and modulate the Th17 cell response during this process.

Abstract Extracellular vesicles (EVs) have been identified as promising biomarkers for the noninvasive diagnosis of various diseases. However, challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low purities. Here, we report a high-yield ( > 90%) and rapid (

Abstract Background The H5N1 influenza virus is a cause of severe pneumonia. Co-infection of influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to poor prognosis of patients during the COVID-19 epidemic. However, reports on patients co-infected with avian influenza virus and SARS-CoV-2 are scarce. Case presentation A 52-year-old woman presented with a fever, which has persisted for the past eight days, along with worsening shortness of breath and decreased blood pressure. Computed tomography (CT) revealed an air bronchogram, lung consolidation, and bilateral pleural effusion. The subsequent polymerase chain reaction (PCR) of the bronchoalveolar lavage fluid (BALF) revealed positivity for H5N1 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Conclusion The H5N1 influenza virus is a cause of severe pneumonia. The clinical presentation of the patient had a predomination of H5N1 influenza rather than COVID-19. A PCR analysis for the identification of the virus is necessary to reveal the pathogen causing the severe pneumonia. The patient exhibited an excellent prognosis upon the use of the appropriate antiviral medicine.

Abstract There are lots of researches on fixture layout optimization for large thin-walled parts. Current researches focus on the positioning problem, i.e., optimizing the positions of a constant number of fixtures. However, how to determine the number of fixtures is ignored. In most cases, the number of fixtures located on large thin-walled parts is determined based on engineering experience, which leads to huge fixture number and extra waste. Therefore, this paper constructs an optimization model to minimize the number of fixtures. The constraints are set in the optimization model to ensure that the part deformation is within the surface profile tolerance. In addition, the assembly gap between two parts is also controlled. To conduct the optimization, this paper develops an improved particle swarm optimization (IPSO) algorithm by integrating the shrinkage factor and adaptive inertia weight. In the algorithm, particles are encoded according to the fixture position. Each dimension of the particle is assigned to a sub-region by constraining the optional position range of each fixture to improve the optimization efficiency. Finally, a case study on ship curved panel assembly is provided to prove that our method can optimize the number of fixtures while meeting the assembly quality requirements. This research proposes a method to optimize the number of fixtures, which can reduce the number of fixtures and achieve deformation control at the same time.

Abstract Background The priority effect of plant arrival is a key driver of community assembly and ecosystem succession during the restoration of degraded plant communities. However, the significance of the arrival order of different plant functional groups and their interactions with community assemblies remains unclear. Using a phytotron experiment with three fully crossed factors, we investigated the underlying mechanisms of priority effects and their relationships with the biomass and biodiversity effects in mixed plant communities by manipulating the order of arrival of species, isolation of roots, and removal of specific plants. Results The results showed that the strength and direction of priority effects were influenced by arrival order, root interactions, asymmetric competition among species, and their interactions. The identities of early and late-sown species also determined the magnitude of priority effects. The priority effects were stronger in grass-first (24.76%) and legume-first communities (24.48%) than in forb-first communities. The pot biomass of the different priority treatments was highest in grass-first (5.85 g), followed by legume-first (3.94 g) and forb-first (2.48 g). The order of arrival in the mixture significantly affected the net biodiversity effects (P

Background & Aims: Metabolic dysfunction–associated steatohepatitis (MASH) is a common chronic liver disease worldwide. No effective pharmacologic therapies for MASH have been developed; to develop such promising drugs, the underlying mechanisms regulating MASH need to be elucidated. Here, we aimed to determine the role of ovarian tumor domain-containing protein 5 (OTUD5) in MASH progression and identify a specific mechanism. Methods: The expression levels of OTUD subfamily under palmitic acid/oleic acid (PAOA) stimulation were screened. OTUD5 expression was assessed in human liver tissues without steatosis, those with simple steatosis, and those with MASH. MASH models were developed in hepatocyte-specific Otud5-knockout mice that were fed high-fat high-cholesterol and high-fat high-cholesterol plus high-fructose/sucrose diet for 16 weeks. Results: The expression of OTUD5 was down-regulated in fatty liver and was negatively related to the progression of MASH. Lipid accumulation and inflammation were exacerbated by Otud5 knockdown but attenuated by Otud5 overexpression under PAOA treatment. Hepatocyte-specific Otud5 deletion markedly exacerbated steatosis, inflammation, and fibrosis in the livers of 2 MASH mouse models. We identified voltage-dependent anion channel 2 (VDAC2) as an OTUD5-interacting partner; OTUD5 cleaved the K48-linked polyubiquitin chains from VDAC2, and it inhibited subsequent proteasomal degradation. The anabolic effects of OTUD5 knockdown on PAOA-induced lipid accumulation were effectively reversed by VDAC2 overexpression in primary hepatocytes. Metabolomic results revealed that VDAC2 is required for OTUD5-mediated protection against hepatic steatosis by maintaining mitochondrial function. Conclusions: OTUD5 may ameliorate MASH progression via VDAC2-maintained mitochondrial homeostasis. Targeting OTUD5 may be a viable MASH-treatment strategy.

Ultra-compact passive phase shifters are inversely designed by the multi-objective particle swarm optimization algorithm. The wavelength-dependent phase difference between two output beams originates from the different distances of the input light passing through the 4 μm × 3.2 μm rectangular waveguide with random-distributed air-hole arrays. As the wavelength changes from 1535 to 1565 nm, a phase difference tuning range of 6.26 rad and 6.95 rad is obtained for TE and TM modes, respectively. Compared with the array waveguide grating counterpart, the phase shifters exhibit higher transmission with a much smaller footprint. By combining the inverse-designed phase shifter and random-grating emitter together, integrated beam-steering structures are built, which show a large scanning range of ±25.47° and ±27.85° in the lateral direction for TE and TM mode, respectively. This work may pave the way for the development of ultra-compact high-performance optical phased array LiDARs.

There are various types of land use in the agricultural and pastoral areas of northern China, including natural grassland and artificial grassland, scrub land, forest land and farmland, may change the soil microbial community However, the soil microbial communities in these different land use types remain poorly understood. In this study, we compared soil microbial communities in these five land use types within the agro-pastoral ecotone of northern China. Our results showed that land use has had a considerable impact on soil bacterial and fungal community structures. Bacterial diversity was highest in shrubland and lowest in natural grassland; fungal diversity was highest in woodland. Microbial network structural complexity also differed significantly among land use types. The lower complexity of artificial grassland and farmland may be a result of the high intensity of anthropogenic activities in these two land-use types, while the higher structural complexity of the shrubland and woodland networks characterised by low-intensity management may be a result of low anthropogenic disturbance. Correlation analysis of soil properties (e.g., soil physicochemical properties, soil nutrients, and microbiomass carbon and nitrogen levels) and soil microbial communities demonstrated that although microbial taxa were correlated to some extent with soil environmental factors, these factors did not sufficiently explain the microbial community differences among land use types. Understanding variability among soil microbial communities within agro-pastoral areas of northern China is critical for determining the most effective land management strategies and conserving microbial diversity at the regional level.

BackgroundTillage practices can substantially affect soil properties depending on crop stage. The interaction between tillage and crop growth on arbuscular mycorrhizal fungi (AMF) communities remains unclear. We investigated the interactions between four tillage treatments (CT: conventional tillage, RT: reduced tillage, NT: no tillage with mulch, and SS: subsoiling with mulch), maintained for 25 years, and two wheat growth stages (elongation stage and grain filling stage) on AMF diversity and community composition.ResultsThe AMF community composition strongly changed during wheat growth, mainly because of changes in the relative abundance of dominant genera Claroideoglomus, Funneliformi, Rhizophagu, Entrophospora, and Glomus. Co-occurrence network analysis revealed that the grain filling stage had a more complex network than the elongation stage. Redundancy analysis results showed that keystone genera respond mainly to changes in soil organic carbon during elongation stage, whereas the total nitrogen content affected the keystone genera during grain filling. Compared with CT, the treatments with mulch, i.e., NT and SS, significantly changed the AMF community composition. The change of AMF communities under different tillage practices depended on wheat biomass and soil nutrients. NT significantly increased the relative abundances of Glomus and Septoglomus, while RT significantly increased the relative abundance of Claroideoglomus.ConclusionOur findings indicate that the relative abundance of dominant genera changed during wheat growth stages. Proper tillage practices (e.g., NT and SS) benefit the long-term sustainable development of the Loess Plateau cropping systems.

Abstract Background Currently there is no specific molecular biomarker for the diagnosis and treatment of renal cell carcinoma (RCC). Here we performed a gender‐specific two‐sample Mendelian randomization analysis to systematically assess the effects of circulating cytokines on RCC. Methods We have employed cis‐quantitative trait loci as instrumental variables for the protein levels and expression of circulating cytokines. We estimated the causal effects of circulating cytokines on RCC risk in males and females with several Mendelian randomization methods. Results We observed a significant causal effect of Eotaxin on the increased risk of RCC in males (Odds ratio [OR] = 2.546, 95% confidence interval [CI] = 1.617–4.010, p value = 5.496 × 10–5), but not in females (OR = 1.352, 95% CI = 0.766–2.388, p value = 0.298). Besides, we also identified several cytokines as potentially associated with RCC in males including RANTES, MCP3, PDGFbb, TRAIL, and several other cytokines as potentially associated with RCC in females including sICAM and SCGFb. Conclusion Our study highlighted that a higher level of circulating Eotaxin is causally associated with an increased risk of RCC in males but not in females. Further studies are needed to elucidate the exact mechanism and its potential application in the prognosis and treatment of RCC.

Abstract While mesenchymal stem cells (MSCs) have gained enormous attention due to their unique properties of self-renewal, colony formation, and differentiation potential, the MSC secretome has become attractive due to its roles in immunomodulation, anti-inflammatory activity, angiogenesis, and anti-apoptosis. However, the precise stimulation and efficient production of the MSC secretome for therapeutic applications are challenging problems to solve. Here, we report on Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs: AIMS. We create an acoustofluidic mechanobiological environment to form reproducible three-dimensional MSC aggregates, which produce the MSC secretome with high efficiency. We confirm the increased MSC secretome is due to improved cell-cell interactions using AIMS: the key mediator N-cadherin was up-regulated while functional blocking of N-cadherin resulted in no enhancement of the secretome. After being primed by IFN-γ, the secretome profile of the MSC aggregates contains more anti-inflammatory cytokines and can be used to inhibit the pro-inflammatory response of M1 phenotype macrophages, suppress T cell activation, and support B cell functions. As such, the MSC secretome can be modified for personalized secretome-based therapies. AIMS acts as a powerful tool for improving the MSC secretome and precisely tuning the secretory profile to develop new treatments in translational medicine.

Oil content and the movability of shale oil are important indicators for the evaluation of continental shale oil. In recent years, the sandwiched shale oil in the fourth member of the Shahejie Formation in the Liaohe Western Depression area of the Bohai Bay Basin has shown great exploration potential, while the understanding of shale oil content and the movability of shale oil is weak. In this study, through a combination of core observations and experiments, we clarified the shale lithofacies types in the fourth member of the Shahejie Formation in the Liaohe Western Depression and explored the influencing factors of the characteristics in the oil-bearing and movability of shales in different lithofacies. The results of the study show that the organic matter content of the shale is high (TOC = 2.2–4.3%), but the maturity of thermal evolution is low (Ro = 0.38–0.55%), and the mineral component is dominated by clay minerals (30.3–72.7%), with quartz, feldspar, and other feldspar minerals developing secondarily. According to the content of organic matter, the mineral component, and the sedimentary structure, five types of lithofacies can be classified: organic-rich laminated clay-bearing felsic shale lithofacies (LS1), organic-rich laminated clay felsic mixed shale lithofacies (LS2), organic-rich layered clay felsic mixed shale lithofacies (LS3), organic-containing massive felsic-bearing clay shale lithofacies (LS4), and organic-containing massive clay felsic mixed shale lithofacies (LS5). The oil content of shale is mainly affected by the organic matter. The rate of increase in oil content of shale is fastest when the organic matter content is between 2 and 4%. The movability of shale oil is mainly controlled by the sedimentary structure, mineral component, and microscopic pore structure; the more the shale laminae is developed, the lower the clay content is, and the more the pore space is developed, the better the movability of shale oil is. Combined with the results of the shale oil content and mobility analysis in the study area, LS2 and LS3 are the dominant lithofacies in the fourth member of the Shahejie Formation in the study area, followed by LS1 >LS5 >LS4, so shale oil exploration should focus on the development of LS2 and LS3.

Abstract Background Saccharomyces cerevisiae has been used in the biosynthesis of acid products such as organic acids owing to its acid tolerance. Improving the acid tolerance of S. cerevisiae is beneficial for expanding its application range. Our previous study isolated the TAMC strain that was tolerant to a pH 2.3 through adaptive laboratory evolution; however, its mechanism underlying tolerance to low pH environment remains unclear. Results In this study, through visual observation and order analysis of plasma membrane and membrane microdomains, we revealed that the membrane microdomains of TAMC strain play an indispensable role in acid tolerance. Transcriptomic analysis showed an increase in the expression of genes related to key components of membrane microdomains in TAMC strain. Furthermore, an obvious reduction was observed in the acid tolerance of the strain with sterol C-24 methyltransferase encoding gene ERG6 knockout for inhibiting membrane microdomain formation. Finally, colocalization analysis of H+-ATPase PMA1 and plasma membrane protein PMP1 showed that disruption of membrane microdomains could inhibit the formation of the H+-ATPase complex. Conclusions Membrane microdomains could provide a platform for forming H+-ATPase complexes to facilitate intracellular H+ homeostasis, and thereby improve cell acid resistance. This study proposed a novel acid tolerance mechanism, providing a new direction for the rational engineering of acid-tolerant strains.

Abstract To investigate the unmet needs for rehabilitation services among middle-aged and older adults in Chengdu, Sichuan, China, and identify the associated factors. This cross-sectional study was conducted on middle-aged and older adults in Chengdu, Sichuan, China, between 2015 and 2016. The questionnaire included demographic data and questions about rehabilitation needs. Multivariable logistic regression analysis was used to identify the associated factors of unmet needs for rehabilitation services. Among 663 participants, 91.70% needed medical rehabilitation (608/663), 26.55% of who need auxiliary equipment (176/663), 77.07% of who need daily care and social participation (511/663), and 79.34% of who need recreational therapy activities (526/663), while

Abstract Breeding rapeseed varieties with more main inflorescence siliques is an idea for developing rapeseed varieties that are suitable for light and simplified cultivation. The Brassica napus exhibited cluster bud of the main inflorescence (Bnclib) gene. At the fruiting stage, the main inflorescence had more siliques, higher density, and more main inflorescences. Moreover, the top of the main inflorescence bifurcated. Genetic analysis showed that the separation ratio between Bnclib and the wild type in the F2 generation was 3:1, which indicated that the trait was a single-gene-dominant inheritance. Among the 24 candidate genes, only one gene, BnaA03g53930D, showed differential expression between the groups (False discovery rate, FDR ≤ 0.05, |log2FC|≤ 1). qPCR verification of the BnaA03g53930D gene between Huyou 17 and its Bnclib near-isogenic line showed that BnaA03g53930D was significantly differentially expressed in the stem tissue of Huyou 17 and its Bnclib near-isogenic line (Bnclib NIL). The determination of gibberellin (GA), brassinolide (BR), cytokinin (CTK), jasmonic acid (JA), growth hormone (IAA), and strigolactone (SL) content in the shoot apex of Huyou 17 by Bnclib NIL and wild type showed that all six hormones significantly differed between the Bnclib NIL and Huyou 17. It is necessary to conduct further research on the interactions between JA and the other five hormones and the main inflorescence bud clustering in B. napus.

Nitrogen (N) and phosphorus (P) are key components in biogeochemical cycling and considerable efforts have been made to understand the effects of their availability on microbial biomass. Nevertheless, the interplay between N and P supply in modulating soil microbes remains unclear. We conducted a comprehensive global analysis of 108 studies spanning boreal to tropical regions to evaluate their interactive impacts on microbial biomass. The findings revealed a significant decrease in microbial biomass with N addition, whereas P supplementation resulted in a notable increase in microbial biomass. Among the observed interactive effects, additive effects were predominant. More importantly, we found that among all of the assessed factors, the impacts of N-P interaction on soil microorganisms are dependent on changes in soil pH. In conclusion, our findings provide valuable insights into the interactive effects of N and P enrichment on microbial biomass. These findings will contribute to the development of global models that predict the impacts of N and P enrichment on soil microbes and ecosystem functions.

Global warming has increased the probability of extreme climate events, with compound extreme events having more severe impacts on socioeconomics and the environment than individual extremes. Utilizing the Coupled Model Intercomparison Project Phase 6 (CMIP6), we predicted the spatiotemporal variations of compound extreme precipitation-high temperature events in China under three Shared Socioeconomic Pathways (SSPs) across two future periods, and analyzed the changes in exposed populations and identified influencing factors. From the result, we can see that, the CMIP6 effectively reproduces precipitation patterns but exhibits biases. The frequency of compound event rises across SSPs, especially under high radiative forcing, with a stronger long-term upward trend. Furthermore, the economically developed areas, notably China's southeastern coast and North China Plain, will be hotspots for frequent and intense compound extreme events, while other regions will see reduced exposure. Finally, in the long-term future (2070-2100), there is a noteworthy shift in population exposure to compound events, emphasizing the increasing influence of population factors over climate factors. This highlights the growing importance of interactions between population and climate in shaping exposure patterns.

Abstract Neonatal subpial hemorrhage is a poorly understood type of intracranial hemorrhage. Herein, we reported on 34 neonates with subpial hemorrhages, focusing on the imaging features, clinical factors, and outcomes of this type of intracranial hemorrhage. This retrospective case series enrolled 34 neonates with subpial hemorrhages. We analyzed their magnetic resonance (MR) images, clinical manifestations, and prognoses. We categorized, for the first time, the MR images of patients with subpial hemorrhages into three imaging patterns; moreover, on the basis of a yin-yang sign, we added a sandwich sign, attaining an MR image feature that was easier to understand. MR Patterns A and B both have good prognoses, and most patients had normal clinical outcomes. Subpial hemorrhage in neonates may be diagnosed via imaging patterns. Recognizing this pattern of hemorrhage may help gain a better understanding of the associated risk factors.

Abstract Aims Acute viral myocarditis (AVMC) is the aetiology of heart failure (HF) with few specific treatments. The improvement of left ventricular ejection fraction (LVEF) is a critical predictor for the prognosis of AVMC. LCZ696 is a drug used in HF to improve LVEF, with a few research on AVMC. In this research, we evaluated the effects and mechanism of LCZ696 in improving LVEF in AVMC. Methods Eighty 4‐week‐old male BALB/c mice were randomly divided into four groups of 20: Sham; Sham + LCZ696 (60 mg/kg/d); AVMC; AVMC + LCZ696. The above experiments were repeated by CVB3‐infected HL‐1 and Mdivi‐1 to down‐regulated dynamin‐related protein 1(Drp1). Adeno‐associated virus 9 (AAV9) with enhanced green fluorescent proteins (GFP) was injected to produce Drp1‐overexpression mice and set up four groups: AVMC group, AVMC + AAV group, AVMC + LCZ696 group, and AVMC + LCZ696 + AAV group (n = 20 in each group). LVEF was evaluated by echocardiography at a similar heart rate (HR) at d7, Drp1 (p‐Drp1), inflammation and apoptosis by histology and Western blot (WB), and mitochondrial by electron microscopy. Results Cardiac function were injured in AVMC that LCZ696 reversed (LVEF, %: Sham: 68.99 ± 9.67; Sham + LCZ696: 71.96 ± 6.20; AVMC: 30.95 ± 6.40*; AVMC + LCZ696: 68.99 ± 9.67*#, *P

Abstract Objective This study aimed to apply radiomics analysis of the change of deep medullary veins (DMV) on susceptibility-weighted imaging (SWI), and to distinguish mild hypoxic-ischemic encephalopathy (HIE) from moderate-to-severe HIE in neonates. Methods A total of 190 neonates with HIE (24 mild HIE and 166 moderate-to-severe HIE) were included in this study. All of them were born at 37 gestational weeks or later. The DMVs were manually included in the regions of interest (ROI). For the purpose of identifying optimal radiomics features and to construct Rad-scores, 1316 features were extracted. LASSO regression was used to identify the optimal radiomics features. Using the Red-score and the clinical independent factor, a nomogram was constructed. In order to evaluate the performance of the different models, receiver operating characteristic (ROC) curve analysis was applied. Decision curve analysis (DCA) was implemented to evaluate the clinical utility. Results A total of 15 potential predictors were selected and contributed to Red-score construction. Compared with the radiomics model, the nomogram combined model incorporating Red-score and urea nitrogen did not better distinguish between the mild HIE and moderate-to-severe HIE group. For the training cohort, the AUC of the radiomics model and the combined nomogram model was 0.84 and 0.84. For the validation cohort, the AUC of the radiomics model and the combined nomogram model was 0.80 and 0.79, respectively. The addition of clinical characteristics to the nomogram failed to distinguish mild HIE from moderate-to-severe HIE group. Conclusion We developed a radiomics model and combined nomogram model as an indicator to distinguish mild HIE from moderate-to-severe HIE group.

In computed tomography (CT) imaging, artifacts will degrade the quality of reconstructed images. To solve this issue, in this paper we propose a method to remove concentric elliptical artifacts from CT images. This method is based on the idea of Directional total variation (DTV), which models the problem of elliptical artifact removal as an energy minimization problem, and establishes a variation-based model which is adapted the elliptical artifacts by analyzing the edge features of elliptical artifacts. Since the proposed model is a non-smooth convex optimization problem with a divisible structure, the alternating direction multiplier method (ADMM) is applied. Finally, the effectiveness of the model in removing elliptical artifacts is verified by simulation experiments.

Highlights 4-Terminal inorganic perovskite/organic tandem solar cells were made by using semi-transparent inorganic perovskite solar cells and narrow-bandgap organic solar cells as the sub-cells, yielding a power conversion efficiency of 22.34%, which is the highest efficiency for inorganic perovskite/organic tandem solar cells. Inorganic perovskite solar cells made by drop-coating (self-spreading) gave much higher power conversion efficiency than the cells made by spin-coating, enabling perovskite/organic tandem solar cells with higher efficiency.

Abstract Multiple false target jamming is an effective electronic attack measurement that will deteriorate the detection performance of radar constant false alarm rate (CFAR) detector, but its effects lack sufficient exploration. To solve the problem, an upgraded Bernoulli experiment model (BEM) is established and deduced using direct integral method. Given the number of jamming pulses in different cells, the detection performance can be obtained analytically. BEM can provide a meaningful physical view of CFAR from energy perspective, unveiling the mechanism how jamming deteriorate CFAR performance. Real multiple false target jamming is an extension of BEM where pulses are randomly located. This can be solved by integrating the distribution of jamming pulses into BEM which is named as statistical model (SM). Numerical examples validate that BEM and SM are more accurate and thousands of times faster than Monte‐Carlo results. Influential parameters are discussed and some valuable suggestions for radar counter‐countermeasurement are obtained.

The purpose of this experiment was to investigate the effects of Litsea cubeba essential oil (LCO) on the growth performance, blood antioxidation, immune function, apparent digestibility of nutrients, and fecal microflora in fattening pigs. A total of 120 pigs were randomly assigned to five groups, with six replicate pens per treatment and four pigs per pen, and they were fed basal diet, chlortetracycline (CTC), and low-, medium-, and high-concentration LCO. The results of the study showed that compared with the control treatment and CTC addition treatment of the basic diet, the catalase level in the serum of the pigs treated with 500 mg/kg LCO in the diet of finishing pigs was significantly increased (p < 0.05). The apparent digestibility of crude protein, crude ash, and calcium in pigs with different levels of LCO was significantly increased compared with the control treatments fed the basal diet (p < 0.05). In addition, compared with the control treatment fed the basal diet and the treatment with CTC, the apparent digestibility of ether extract in pigs treated with medium-dose LCO was significantly increased (p < 0.05), and the apparent digestibility of pigs was significantly increased after the addition of low-dose LCO (p < 0.05). Among the genera, the percentage abundance of SMB53 (p < 0.05) was decreased in the feces of the CTC group when compared to that in the medium-LCO group. At the same time, the relative abundance of L7A_E11 was markedly decreased in the feces of the control and medium- and high-concentration LCO group than that in the CTC group (p < 0.05). In conclusion, adding the level of 250 mg/kg LCO in the diet of pig could improve the growth performance and blood physiological and biochemical indicators of pigs, improve the antioxidant level of body and the efficiency of digestion and absorption of nutrients, and show the potential to replace CTC.

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by the Dabie bandavirus (DBV), and it has become a global public health threat. Cytokine storm is considered to be an important pathogenesis of critical SFTS. Tripartite motif-containing 3 (TRIM3), as a member of the TRIM protein family, may contribute to the regulation of the immune and inflammatory responses after viral infection. However, whether TRIM3 plays a major role in the pathogenesis of SFTS has not yet been investigated.MethodsTRIM3 mRNA levels were detected in PBMCs between 29 SFTS patients and 29 healthy controls by qRT-PCR. We established the pathogenic IFNAR−/− SFTS mouse model successfully by inoculating subcutaneously with DBV and testing the expression levels of TRIM3 mRNA and protein by qRT-PCR and immunofluorescence in the livers, spleens, lungs, and kidneys. TRIM3OE THP-1 cells and peritoneal macrophages extracted from TRIM3−/− mice were infected with DBV. The effect of TRIM3 on cytokines was detected by qRT-PCR and ELISA. Then we examined Toll-like receptor 3 (TLR3) and protein phosphorylation in the MAPK pathway after DBV infection using Western blot. Flow cytometry was used to verify TLR3 expression on peripheral blood monocytes in SFTS patients. We further explored the interaction between TRIM3 and TLR3 using CO-IP and Western blot.ResultsCompared to healthy controls, TRIM3 mRNA expression in PBMCs is decreased in SFTS patients, especially in severe cases. TRIM3 mRNA and protein were synchronously reduced in the livers, spleens, lungs, and kidney tissues of the IFNAR−/− SFTS mice model. In the DBV-infected cell model, TRIM3 overexpression can inhibit the DBV-induced release of IL-1β, IL-6, and TNF-α, the expression of TLR3, and protein phosphorylation in the MAPK pathway, which plays an anti-inflammatory role, while TRIM3 deficiency exacerbates the pro-inflammatory effects. We further found that TRIM3 can promote TLR3 degradation through K48-linked ubiquitination.ConclusionTRIM3 can inhibit the production of cytokines by regulating the degradation of TLR3 through K48-linked ubiquitination, which can be a therapeutic target for improving the prognosis of SFTS.

High-precision temperature control of large-area blackbodies has a pivotal role in temperature calibration and thermal imaging correction. Meanwhile, it is necessary to correct the temperature difference between the radiating (surface of use) and back surfaces (where the temperature sensor is installed) of the blackbody during the testing phase. Moreover, large-area blackbodies are usually composed of multiple temperature control channels, and manual correction in this scenario is error-prone and inefficient. At present, there is no method that can achieve temperature-automated calibration for a large-area blackbody radiation source. Therefore, this article is dedicated to achieving temperature-automated calibration for a large-area blackbody radiation source. First, utilizing two calibrated infrared thermometers, the optimal temperature measurement location was determined using a focusing algorithm. Then, a three-axis movement system was used to obtain the true temperature at the same measurement location on a large-area blackbody surface from different channels. This temperature was subtracted from the blackbody’s back surface. The temperature difference was calculated employing a weighted algorithm to derive the parameters for calibration. Finally, regarding experimental verification, the consistency error of the temperature measurement point was reduced by 85.4%, the temperature uniformity of the surface source was improved by 40.4%, and the average temperature measurement deviation decreased by 43.8%. In addition, this system demonstrated the characteristics of strong environmental adaptability that was able to perform temperature calibration under the working conditions of a blackbody surface temperature from 100 K to 573 K, which decreased the calibration time by 9.82 times.

Abstract Background Cranial fasciitis (CF) is a rare benign fibroproliferative lesion of the skull. To date, the summarized radiologic characteristics and the subtype of the disease have not been reported. our purpose was to summarize the characteristic clinicoradiology features and management of CF and to improve the knowledge of radiologists and clinicians. Methods We searched our institution’s database and retrieved the clinical and radiologic data of CF patients confirmed by histopathological examination. The clinicoradiology features and management of CF were analysed retrospectively. Results A total of 14 CF patients were included. A total of 85.7% of the patients presented with a painless, firm, nonmobile and single mass. Tenderness and multiple masses were found in 14.3% of the patients. The mass was clearly increased in 2 patients and gradually increased in 5 patients in the short term. We divided these patients into three types based on the CT characteristics. The characteristic features of type I (9 patients) presented as an expansive and osteolytic bone destruction with a soft tissue mass. Type II (2 patients) presented as a scalp mass with mild erosion of the outer skull plate. Type III (3 patients) presented as a scalp mass without skull destruction. All patients underwent surgical resection. For type I patients, craniectomy and cranioplasty were performed. For type II patients, complete excision of the scalp mass with local skull curettage was performed. For type III patients, complete excision of the scalp mass was performed. There were no cases of recurrence after follow-up. Conclusions CF usually presents as a painless, firm, nonmobile and single mass with a clear boundary. There are generally three types of MSCT findings: bone destruction with a soft tissue mass, a scalp mass with erosion of the skull and a scalp mass. Different management strategies should be utilized for the various types of CF.

Abstract At the single-cell level, cellular parameters, gene expression and cellular function are assayed on an individual but not population-average basis. Essential to observing and analyzing the heterogeneity and behavior of these cells/clusters is the ability to prepare and manipulate individuals. Here, we demonstrate a versatile microsystem, a stereo acoustic streaming tunnel, which is triggered by ultrahigh-frequency bulk acoustic waves and highly confined by a microchannel. We thoroughly analyze the generation and features of stereo acoustic streaming to develop a virtual tunnel for observation, pretreatment and analysis of cells for different single-cell applications. 3D reconstruction, dissociation of clusters, selective trapping/release, in situ analysis and pairing of single cells with barcode gel beads were demonstrated. To further verify the reliability and robustness of this technology in complex biosamples, the separation of circulating tumor cells from undiluted blood based on properties of both physics and immunity was achieved. With the rich selection of handling modes, the platform has the potential to be a full-process microsystem, from pretreatment to analysis, and used in numerous fields, such as in vitro diagnosis, high-throughput single-cell sequencing and drug development.

Understanding the factors that hamper immune therapy in breast cancer may increase the range of patients who benefit. Here authors show that breast cancer cells produce and subsequently transfer active TGF-β type II receptors to CD8 + T cells to render them exhausted, thus paralyzing the anti-tumor immune response.

Highlights Biochar amendment significantly increased DNRA rate in the paddy soil. Increased DNRA rate was due to enhanced C availability and enriched DNRA bacteria. Biochar amendment shifted more nitrate partitioning toward DNRA process. Potential of straw-derived biochar in alleviating N loss was superior to straw itself.

ObjectivesInvasive pulmonary aspergillosis (IPA) is common in immuno-compromised people, and a high incidence of IPA has been found in patients with severe fever with thrombocytopenia syndrome (SFTS). Our study aimed to determine the independent risk factors for IPA and the relationship between smoking status and the risk of IPA in SFTS patients.MethodsA retrospective analysis of SFTS patients in the First Affiliated Hospital of Nanjing Medical University from May 2011 to December 2021 was reviewed. The patients were divided into two groups: IPA and non-IPA groups. We compared demographic characteristics, clinical manifestation, laboratory parameters, treatment, and prognosis, and explored the risk factors of IPA using logistic regression and ROC curve. The dose-dependent effect of smoking on the risk of IPA was further estimated, including the age of smoking initiation, daily smoking amount, smoking duration, and pack-years of smoking.ResultsIn total, 189 individuals were included. Compared with the non-IPA group, the IPA group had higher levels of smoking, drinking, cough, dyspnea, aCCI scores, Dabie bandavirus (DBV) RNA load, ferritin, PCT, IL-6, APTT, LDH, BUN, creatinine, and lower levels of FT4 and TSH. The incidences of MODS, admission to ICU, ventilation, and broad-spectrum antibiotic treatment were significantly higher in the IPA group than in the non-IPA group. Multivariable logistic analysis showed that smoking history, cough, creatinine, admission to ICU, broad-spectrum, and corticosteroid therapies were the independent risk factors for IPA in SFTS patients. We further confirmed that the age of smoking initiation

BackgroundMyelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a newly defined autoimmune inflammatory demyelinating central nervous system (CNS) disease characterized by antibodies against MOG. Leptomeningeal enhancement (LME) on contrast-enhanced fluid-attenuated inversion recovery (CE-FLAIR) images has been reported in patients with other diseases and interpreted as a biomarker of inflammation. This study retrospectively analyzed the prevalence and distribution of LME on CE-FLAIR images in children with MOG antibody-associated encephalitis (MOG-E). The corresponding magnetic resonance imaging (MRI) features and clinical manifestations are also presented.MethodsThe brain MRI images (native and CE-FLAIR) and clinical manifestations of 78 children with MOG-E between January 2018 and December 2021 were analyzed. Secondary analyses evaluated the relationship between LME, clinical manifestations, and other MRI measures.ResultsForty-four children were included, and the median age at the first onset was 70.5 months. The prodromal symptoms were fever, headache, emesis, and blurred vision, which could be progressively accompanied by convulsions, decreased level of consciousness, and dyskinesia. MOG-E showed multiple and asymmetric lesions in the brain by MRI, with varying sizes and blurred edges. These lesions were hyperintense on the T2-weighted and FLAIR images and slightly hypointense or hypointense on the T1-weighted images. The most common sites involved were juxtacortical white matter (81.8%) and cortical gray matter (59.1%). Periventricular/juxtaventricular white matter lesions (18.2%) were relatively rare. On CE-FLAIR images, 24 (54.5%) children showed LME located on the cerebral surface. LME was an early feature of MOG-E (P = 0.002), and cases without LME were more likely to involve the brainstem (P = 0.041).ConclusionLME on CE-FLAIR images may be a novel early marker among patients with MOG-E. The inclusion of CE-FLAIR images in MRI protocols for children with suspected MOG-E at an early stage may be useful for the diagnosis of this disease.

Abstract Microbial cell factories for terpenoid synthesis form a less expensive and more environment-friendly approach than chemical synthesis and extraction, and are thus being regarded as mainstream research recently. Organelle compartmentalization for terpenoid synthesis has received much attention from researchers owing to the diverse physiochemical characteristics of organelles. In this review, we first systematically summarized various compartmentalization strategies utilized in terpenoid production, mainly plant terpenoids, which can provide catalytic reactions with sufficient intermediates and a suitable environment, while bypassing competing metabolic pathways. In addition, because of the limited storage capacity of cells, strategies used for the expansion of specific organelle membranes were discussed. Next, transporter engineering strategies to overcome the cytotoxic effects of terpenoid accumulation were analyzed. Finally, we discussed the future perspectives of compartmentalization and transporter engineering strategies, with the hope of providing theoretical guidance for designing and constructing cell factories for the purpose of terpenoid production.

Abstract Background Cryptococcal meningitis (CM) has a high morbidity and mortality due to the low detection of Cryptococcus in cerebrospinal fluid (CSF) during the early stage of the disease with traditional methods. Case presentation In addition to the traditional methods of India ink staining and cryptococcal antigen (CrAg), we used nanopore sequencing and next-generation sequencing (NGS) to detect pathogenic DNA in CSF samples of three patients with CM. The CSF samples of all three patients were positive by India ink staining and CrAg. NGS also detected Cryptococcus in all three CSF samples. Nanopore sequencing detected Cryptococcus in two CSF samples. Conclusion Nanopore sequencing may be useful in assisting with the clinical diagnosis of CM. Further research is needed to determine the sensitivity and specificity of nanopore sequencing of CSF.

Abstract Objective To describe the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children. Method Data from 11 pediatric patients with autoimmune GFAP astrocytopathy were retrospectively analyzed. Results All of the patients showed encephalitis and meningoencephalitis or meningoencephalomyelitis with or without myelitis. 45.4% of the patients had fever, 27.3% headaches, 18.2% dizziness, 18.2% drowsiness, and 18.2% mental disorders. Cerebrospinal fluid (CSF) was detected in all patients. The white blood cell counts (WBC) (90.9%), lactic dehydrogenase levels (72.7%), protein level (36.4%), and adenosine deaminase activity (ADA) level (27.3%) were elevated, and the CSF glucose levels (72.7%) were slightly reduced. Nine patients (90%) were found to have brain abnormalities, of which five (50.0%) patients had abnormal symmetrical laminar patterns or line patterns hyperintensity lesions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images in the basal ganglia, hypothalamus, subcortical white matter and periventricular white matter. The linear radial enhancement pattern of the cerebral white matter was only seen in two patients, with the most common being abnormal enhancement of leptomeninges (50%). Five patients had longitudinally extensive spinal cord lesions. Conclusion The findings of pediatric patients with autoimmune GFAP astrocytopathy are different from previous reports.

This paper considers the time difference of arrival (TDOA) and frequency difference of arrival (FDOA) estimation problem for joint localization using unmanned aerial vehicles (UAVs), involving range migration (RM) and Doppler ambiguity within observation interval. A robust estimation method based on interpolation and resampling is proposed. Specifically, the interpolation artificially increases the pulse repetition frequency (PRF). After that, the resampling eliminates the coupling between range frequency and slow time. Finally, a coherent integration step based on inverse discrete Fourier transform (IDFT) is used to achieve parameter estimation and suppress the grating lobes caused by interpolation. The proposed method could be efficiently implemented by fast Fourier transform (FFT), inverse FFT (IFFT) and non-uniform FFT (NUFFT) without parameter searching procedures. Numerical experiments indicate that the proposed method has nearly optimal anti-noise performance but much lower computational complexity than the maximum likelihood estimator, which makes it more competitive in practical applications.

ObjectiveThe deep medullary veins (DMVs) can be evaluated using susceptibility-weighted imaging (SWI). This study aimed to apply radiomic analysis of the DMVs to evaluate brain injury in neonatal patients with hypoxic-ischemic encephalopathy (HIE) using SWI.MethodsThis study included brain magnetic resonance imaging of 190 infants with HIE and 89 controls. All neonates were born at full-term (37+ weeks gestation). To include the DMVs in the regions of interest, manual drawings were performed. A Rad-score was constructed using least absolute shrinkage and selection operator (LASSO) regression to identify the optimal radiomic features. Nomograms were constructed by combining the Rad-score with a clinically independent factor. Receiver operating characteristic curve analysis was applied to evaluate the performance of the different models. Clinical utility was evaluated using a decision curve analysis.ResultsThe combined nomogram model incorporating the Rad-score and clinical independent predictors, was better in predicting HIE (in the training cohort, the area under the curve was 0.97, and in the validation cohort, it was 0.95) and the neurologic outcomes after hypoxic-ischemic (in the training cohort, the area under the curve was 0.91, and in the validation cohort, it was 0.88).ConclusionBased on radiomic signatures and clinical indicators, we developed a combined nomogram model for evaluating neonatal brain injury associated with perinatal asphyxia.

Background: Sodium—glucose cotransporter 2 inhibitors have proved to be extremely effective and reliable in reducing hyperglycemia, and have also been used for the treatment of cardiovascular and renal disease in patients with or without type 2 diabetes. Thousands of research articles on SGLT2 inhibitors have been published in the past, but few bibliometric analyses have systematically been studied this field. We aimed to visualize the global research hotspots and trends of SGLT2 inhibitors using a bibliometric analysis to provide new evidence and ideas for researchers and clinicians in this field.Methods: We retrieved publications from Science Citation Index Expanded of Web of Science Core Collection in 2004–2022 on 1 July 2022. Microsoft Excel, CiteSpace and VOSviewer were employed to collect publication data, analyze publication trends, and visualize relevant results.Results: We identified 4,419 original research articles on SGLT2 inhibitors published between 2004 and the first half of 2022. Global SGLT2 inhibitors-related research increased rapidly from 2004 to 2022, especially recently. United States made the greatest contribution to the topic, with (1,629, 36.86%) publications and citations (88,892). AstraZeneca was the most prolific institutions (272, 6.16%). Heerspink HJL published the most related articles (98), whereas Zinman B was cited the most frequently (1,784 citations). Diabetes Obesity and Metabolism was the journal with the most studies (406, 9.19%), and The New England Journal of Medicine was the most commonly cited journal (11,617 citations), with nine of the top 10 co-cited references published in this journal. The emerging keywords “heart failure,” “diabetic cardiomyopathy,” “ejection fraction,” “mortality,” “biomarker,” “fibrosis,” “ampk,” and “guideline” appeared the most recently as research frontiers.Conclusion: United States is the leader in SGLT2 inhibitor research. Recently, the research on SGLT2 inhibitors has focused on clinical trials, related mechanisms, and therapy. In the future, the research on SGLT2 inhibitors will delve into molecular mechanisms, especially those related to fibrosis and AMPK, revealing the link between SGLT2 inhibitors and heart failure and diabetic cardiomyopathy will be the next research hotspot.

Abstract The emergence of Y6‐type nonfullerene acceptors has greatly enhanced the power conversion efficiency (PCE) of organic solar cells (OSCs). However, which structural feature is responsible for the excellent photovoltaic performance is still under debate. In this study, two Y6‐like acceptors BDOTP‐1 and BDOTP‐2 were designed. Different from previous Y6‐type acceptors featuring an A–D–Aʹ–D–A structure, BDOTP‐1, and BDOTP‐2 have no electron‐deficient Aʹ fragment in the core unit. Instead, there is an electron‐rich dibenzodioxine fragment in the core. Although this modification leads to a marked change in the molecular dipole moment, electrostatic potential, frontier orbitals, and energy levels, BDOTP acceptors retain similar three‐dimensional packing capability as Y6‐type acceptors due to the similar banana‐shaped molecular configuration. BDOTP acceptors show good performance in OSCs. High PCEs of up to 18.51% (certified 17.9%) are achieved. This study suggests that the banana‐shaped configuration instead of the A–D–Aʹ–D–A structure is likely to be the determining factor in realizing high photovoltaic performance.

IntroductionSevere fever with thrombocytopenia syndrome (SFTS) has become a global threat to public health since its first report in China in 2009. However, the pathogenesis of SFTS virus (SFTSV) in humans remains unclear. Also, there are no effective therapeutics for SFTS. Cyclophilin A (CyPA) regulates protein folding and trafficking involved in various viral infectious diseases, but its role in SFTSV infection has not been elucidated.MethodsWe detected plasma CyPA levels in 29 healthy subjects and 30 SFTS patients by ELISA. In THP-1 cells and normal human peripheral blood mononuclear cells (PBMCs), SFTSV-induced extracellular CyPA (eCyPA) was also detected by ELISA. In THP-1, the effects of CyPA on Mitogen-activated protein kinase (MAPK) pathway and NF-κB were determined by Western blot. We validated the interaction between CypA and CD147 by human recombinant CyPA (hrCyPA) and the CD147 inhibitor. Effects of CyPA inhibitor Cyclosporine A (CsA) on cytokines and SFTSV replication in THP-1 cells was also detected. 8-week-old Interferon-α/β Receptor (IFNAR) knockout (IFNAR-/-) C57BL/6 mice were divided into mock group, 106TCID50 SFTSV (Untreated) group and 106TCID50 SFTSV+CsA (CsA-treated) group. The changes of body weight, animal behavior and survival time of each group were recorded. Blood samples were collected from tail vein regularly. After death, the liver, spleen, lung, kidney and brain were collected for pathological HE staining and SFTSV-NP immunohistochemical staining.ResultsCompared to healthy subjects and SFTS patients in the febrile phase of the disease, plasma CyPA levels in SFTS patients at the multi-organ dysfunction (MOD) phase showed significantly elevated (P < 0.01). Extracellular CyPA activates the MAPK pathway by binding to CD147 in THP-1 infected with SFTSV. CsA inhibits the pro-inflammatory and promoting replication effects of CyPA after SFTSV infection in vitro. In vivo, CsA can prolong the survival time and delay the weight loss of SFTSV mice. CsA reduces multi-organ dysfunction in IFNAR−/− mice infected with SFTSV.DiscussionOur results indicate that CyPA is associated with SFTSV-induced cytokine storm, which can be a potential target for SFTS therapy.

High-quality alfalfa is an indispensable resource for animal husbandry and sustainable development. Its nutritional quality changes dramatically during its life cycle and, at present, no molecular mechanisms for nutrient metabolic variation in alfalfa leaves at different growth stages have been clearly reported. We have used correlation and network analyses of the alfalfa leaf metabolome, proteome, and transcriptome to explore chlorophyll, flavonoid, and amino acid content at two development stages: budding stage (BS) and full-bloom stage (FBS). A high correlation between the expression of biosynthetic genes and their metabolites revealed significant reductions in metabolite content as the plant matured from BS to FBS. l-Glutamate, the first molecule of chlorophyll biosynthesis, decreased, and the expression of HemA, which controls the transformation of glutamyl-tRNA to glutamate 1-semialdehyde, was down-regulated, leading to a reduction in leaf chlorophyll content. Flavonoids also decreased, driven at least in part by increased expression of the gene encoding CYP75B1: flavonoid 3′-monooxygenase, which catalyzes the hydroxylation of dihydroflavonols and flavonols, resulting in degradation of flavonoids. Expression of NITRILASE 2 (NIT2) and Methyltransferase B (metB), which regulate amino acid metabolism and influence the expression of genes of the glycolysis-TCA pathway, were down-regulated, causing amino acid content in alfalfa leaves to decrease at FBS. This study provides new insights into the complex regulatory network governing the content and decrease of chlorophyll, amino acids, flavonoids, and other nutrients in alfalfa leaves during maturation. These results further provide a theoretical basis for the generation of alfalfa varieties exhibiting higher nutritional quality, high-yield cultivation, and a timely harvest.

Enzyme activity plays an important role in soil biochemical processes and is a key factor driving nutrient cycling. Although a great number of studies examined the effects of nitrogen (N) enrichment and water (W) addition on soil enzyme activity, most of them focused on the effect of only one resource and are based on short-term investigations. The separate and interactive effects of long-term changes in nitrogen and water on soil enzyme activity remain largely unexplored. In this study, we demonstrated the responses of two types of soil enzyme, β-1,4-glucosidase (BG) and acid phosphatase (APA), to increased nitrogen and water based on a 16-year experiment conducted in a typical grassland in northern China. The results show that: (1) nitrogen addition inhibited BG and APA in 2019 and 2020; (2) water addition had no significant effect on BG activity, but significantly reduced APA activity in 2020; and (3) redundancy analysis (RDA) showed that nitrogen and water addition affected soil enzyme activity mainly by affecting soil microbial biomass carbon (MBC). The present research offers a comprehensive explanation of how atmospheric nitrogen deposition and precipitation patterns affect the characteristics of microorganisms and the cycling of nutrients in grassland ecosystems.

Abstract Background Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) is a member of the PAS superfamily. Previous studies explored the carcinogenic roles of transcription factor ARNTL2 in human malignancies. However, its roles in ccRCC have not been elucidated. This study sought to explore the roles of ARNTL2 in ccRCC and determine its correlations with tumor immunity. Methods The expression of ARNTL2 was analyzed using the GEO, TCGA and GTEx database, and verified in ccRCC tissue samples and cell lines by qRT-PCR and western blot analysis. Kaplan–Meier survival curve analysis, Cox regression analysis (including univariate and multivariate analysis) was utilized to evaluate the prognostic values of ARNTL2. Potential biological mechanisms of ARNTL2 were explored using GSEA method. Colony formation and wound healing assays were conducted to explore the oncogenic role of ARNTL2 in ccRCC. ssGSEA and xCell algorithm were used to explore the correlation between ARNTL2 expression and tumor immune microenvironment (TIME). Results ARNTL2 was significantly upregulated in ccRCC tissues and cell lines compared to normal kidney tissues and cell line. Enhanced expression of ARNTL2 was strongly linked to advanced clinical stage and unfavorable overall survival in ccRCC. ARNTL2 was determined as an independent prognostic marker through cox regression analysis. A prognostic nomogram was constructed to predict 1-, 3- and 5-year overall survival of ccRCC patients by integrating ARNTL2 expression with other clinicopathologic variables. GSEA analysis showed that focal adhesion, T cell receptor, cell cycle, and JAK-STAT signaling pathway were significantly enriched in high ARNTL2 samples. Silencing of ARNTL2 suppressed the colony formation ability and wound healing efficacy of ccRCC cell lines. xCell analysis showed that high expression level of ARNTL2 exhibited an immune infiltration status similar to CD8 + inflamed ccRCC subtype, which was characterized by high infiltration level of CD8 + T cell and high expression level of the immune escape biomarkers such as PD-L1, PD-L2, PD1 and CTLA4. Conclusion ARNTL2 is an independent adverse predictor of ccRCC patient survival. High expression level of ARNTL2 is associated with immune infiltration, and may be a novel therapeutic target in ccRCC.

Abstract Background Bladder cancer is a frequently diagnosed urinary system tumor, whose mortality remains rising. Minichromosome maintenance eight homologous recombination repair factor (MCM8), a newly discovered MCM family member, has been shown to be required for DNA replication. Unfortunately, little is known concerning the roles of MCM8 in bladder cancer. Methods The present study, we aimed at probing into the impacts and detailed mechanisms of MCM8 in bladder cancer progression. In this study, MCM8 expression level was detected through immunohistochemistry staining (IHC), qRT-PCR and Western blot assay. Silenced MCM8 cell models were constructed by lentivirus transfection. In vitro, the cell proliferation was evaluated by the MTT assay. The wound-healing assay and the transwell assay were utilized to assess the cell migration. Also, the cell apoptosis and the cell cycle were determined by flow cytometry. Moreover, the Human Apoptosis Antibody Array assay was performed to analyze the alterations of apoptosis-related proteins. The in vivo experiments were conducted to verify the effects of MCM8 knockdown on the tumor growth of bladder cancer. Results The results demonstrated that compared with normal adjacent tissues, MCM8 expression in bladder cancer tissues was strongly up-regulated. The up-regulation of MCM8 expression in bladder cancer may be a valuable independent prognostic indicator. Of note, MCM8 inhibition modulated the malignant phenotypes of bladder cancer cells. In terms of mechanism, it was validated that MCM8 knockdown made Akt, P-Akt, CCND1 and CDK6 levels down-regulated, as well as MAPK9 up-regulated. Conclusions Taken together, our study demonstrated an important role of MCM8 in bladder cancer and created a rationale for the therapeutic potential of MCM8 inhibition in human bladder cancer therapy.