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Abstract Magnetic resonance imaging contrast agents can enhance diagnostic precision but often face limitations such as short imaging windows, low tissue specificity, suboptimal contrast enhancement, or potential toxicity, which affect resolution and long-term monitoring. Here, we present a protein contrast agent based on lanmodulin, engineered with a single-point mutation at position 108 from N to D to yield maximum gadolinium binding sites. After loading with Gd3+ ions, the resulting protein complex, LanND-Gd, exhibits efficient renal clearance, high relaxivity, and prolonged renal retention compared to commercial agents. LanND-Gd enables high-performance visualization of whole-body structures and brain vasculature in male mice at a resolution finer than one hundred micrometers. In male ischemia mouse models, LanND-Gd also improves kidney dysfunction monitoring while minimizing risks of neural toxicity or immunogenic reactions. This protein-based contrast agent offers superior image quality, improved biocompatibility, and extended imaging timeframes, promising significant advancements in magnetic resonance-based diagnostics and patient outcomes.

ABSTRACTThe presence of airborne allergenic pollen causes a variety of immune reactions and respiratory diseases, threatening human life in severe cases. Climate change is exacerbating the allergenic pollen-induced health risks and adding a significant economic burden to societies. Despite the pressing threats, vital health-related information is not available to the public to date, and the reshaping of future geographic allergenic pollen patterns remains unknown. To help establish a critical allergenic pollen forecasting capacity, a systematic review was conducted and three promising future directions were identified: (1) resolving heterogeneous urban plant species distribution and phenology using fine-resolution satellite constellations; (2) acquiring ancillary information about allergenic pollen and patient symptoms from emerging geospatial big data, such as social media; (3) deciphering the coupled effect of climate change and urbanization on future geographic patterns and phenology of allergenic species. On this basis, we recommend an optimized workflow that combines real-time pollen monitoring networks with high-resolution vegetation information and weather forecast systems, comprehensively considering the production and diffusion process of pollen to establish advanced prediction models. By focusing on critical knowledge gaps, this review provides much needed insight to propel the allergenic pollen forecasting research and eventually benefit the management of urban public health.

Summary: Background: In order to address the low compliance and dissatisfied specificity of low-dose computed tomography (LDCT), efficient and non-invasive approaches are needed to complement its limitations for lung cancer screening and management. The ASCEND-LUNG study is a prospective two-stage case–control study designed to evaluate the performance of a liquid biopsy-based comprehensive lung cancer screening and post-screening pulmonary nodules management system. Methods: We aimed to develop a comprehensive lung cancer system called Peking University Lung Cancer Screening and Management System (PKU-LCSMS) which comprises a lung cancer screening model to identify specific populations requiring LDCT and an artificial intelligence-aided (AI-aided) pulmonary nodules diagnostic model to classify pulmonary nodules following LDCT. A dataset of 465 participants (216 cancer, 47 benign, 202 non-cancer control) were used for the two models’ development phase. For the lung cancer screening model development, cancer participants were randomly split at a ratio of 1:1 into the train and validation cohorts, and then non-cancer controls were age-matched to the cancer cases in a 1:1 ratio. Similarly, for the AI-aided pulmonary nodules model, cancer and benign participants were also randomly divided at a ratio of 2:1 into the train and validation cohorts. Subsequently, during the model validation phase, sensitivity and specificity were validated using an independent validation cohort consisting of 291 participants (140 cancer, 25 benign, 126 non-cancer control). Prospectively collected blood samples were analyzed for multi-omics including cell-free DNA (cfDNA) methylation, mutation, and serum protein. Computerized tomography (CT) images data was also obtained. Paired tissue samples were additionally analyzed for DNA methylation, DNA mutation, and messenger RNA (mRNA) expression to further explore the potential biological mechanisms. This study is registered with ClinicalTrials.gov, NCT04817046. Findings: Baseline blood samples were evaluated for the whole screening and diagnostic process. The cfDNA methylation-based lung cancer screening model exhibited the highest area under the curve (AUC) of 0.910 (95% CI, 0.869–0.950), followed by the protein model (0.891 [95% CI, 0.845–0.938]) and lastly the mutation model (0.577 [95% CI, 0.482–0.672]). Further, the final screening model, which incorporated cfDNA methylation and protein features, achieved an AUC of 0.963 (95% CI, 0.942–0.984). In the independent validation cohort, the multi-omics screening model showed a sensitivity of 99.2% (95% CI, 0.957–1.000) at a specificity of 56.3% (95% CI, 0.472–0.652). For the AI-aided pulmonary nodules diagnostic model, which incorporated cfDNA methylation and CT images features, it yielded a sensitivity of 81.1% (95% CI, 0.732–0.875), a specificity of 76.0% (95% CI, 0.549–0.906) in the independent validation cohort. Furthermore, four differentially methylated regions (DMRs) were shared in the lung cancer screening model and the AI-aided pulmonary nodules diagnostic model. Interpretation: We developed and validated a liquid biopsy-based comprehensive lung cancer screening and management system called PKU-LCSMS which combined a blood multi-omics based lung cancer screening model incorporating cfDNA methylation and protein features and an AI-aided pulmonary nodules diagnostic model integrating CT images and cfDNA methylation features in sequence to streamline the entire process of lung cancer screening and post-screening pulmonary nodules management. It might provide a promising applicable solution for lung cancer screening and management. Funding: This work was supported by Science, Science, Technology & Innovation Project of Xiongan New Area, Beijing Natural Science Foundation, CAMS Innovation Fund for Medical Sciences (CIFMS), Clinical Medicine Plus X-Young Scholars Project of Peking University, the Fundamental Research Funds for the Central Universities, Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, Peking University People's Hospital Research and Development Funds, National Key Research and Development Program of China, and the fundamental research funds for the central universities.

Shales of the Wufeng-Longmaxi formations in the basin-margin transition zone of southeastern Chongqing, China are characterized by high organic matter content and a significant presence of pyrite development. By examining numerous scanning electron microscope (SEM) images and considering the crystal and aggregate characteristics of minerals, we identified four types of pyrite in the study area: euhedral crystals, irregular aggregates, framboidal aggregates, and metasomatized organisms. Among these types, framboidal aggregates are the most prevalent. The formation mechanism of framboidal pyrite can be categorized into inorganic and organic origins. As inferred from the pyrite characteristics in the study area, the formation mechanism of the metasomatized organisms aligns with the biologically induced mineralization mode of organic origin, whereas the framboidal aggregates are more associated with the biologically controlled mineralization mode of organic origin. This underscores a close relationship between the pyrite formation and organic matter, which in turn indicates that an organic origin is more consistent with the pyrite characteristics observed in this study area. The pyrite morphology can reflect reactive iron concentration. Euhedral pyrite crystals tend to form under a low reactive iron concentration, whereas the formation of framboidal pyrite requires a high reactive iron concentration. Additionally, the type and grain size of pyrite aggregates can reflect variations in the redox conditions of the depositional environment. Pyrite produces positive effects on reservoir storage space, with intercrystalline organic pores, intercrystalline pores, and mold pores associated with pyrite contributing greatly to the storage spaces.

Abstract Understanding how dietary polysaccharides affect mucin O-glycosylation and gut microbiota could provide various nutrition-based treatments. Here, the O-glycan profile of the colonic mucosa and gut microbiome were investigated in C57BL/6J mice fed six structurally diverse dietary polysaccharides and a mixture of six fibers. Dietary polysaccharides increased total O-glycans, mainly by stimulating neutral glycans. Highly branched arabinogalactan promoted terminally fucosylated core 1 O-glycans; whereas linear polysaccharides, including pectin, konjac glucomannan, inulin, and the fiber mixture, favored terminally di-fucosylated O-glycans. The last three polysaccharides also lowered the level of sulfated O-glycans and sialylated mono-fucosylated O-glycans. Varied monosaccharide composition in mixed polysaccharides had a synergistic beneficial effect, boosting fucosylated neutral glycans, decreasing acidic glycans, and stimulating microbial richness and diversity. Dietary polysaccharides containing arabinose and sulfate groups enhanced the relative abundances of Akkermansia and Muribaculaceae, respectively. The present comparison reveals the relationship between dietary polysaccharide structure, mucin O-glycan composition, and intestinal microorganisms.

Abstract Land surface phenology (LSP) products are currently of large uncertainties due to cloud contaminations and other impacts in temporal satellite observations and they have been poorly validated because of the lack of spatially comparable ground measurements. This study provided a reference dataset of gap-free time series and phenological dates by fusing the Harmonized Landsat 8 and Sentinel-2 (HLS) observations with near-surface PhenoCam time series for 78 regions of 10 × 10 km2 across ecosystems in North America during 2019 and 2020. The HLS-PhenoCam LSP (HP-LSP) reference dataset at 30 m pixels is composed of: (1) 3-day synthetic gap-free EVI2 (two-band Enhanced Vegetation Index) time series that are physically meaningful to monitor the vegetation development across heterogeneous levels, train models (e.g., machine learning) for land surface mapping, and extract phenometrics from various methods; and (2) four key phenological dates (accuracy ≤5 days) that are spatially continuous and scalable, which are applicable to validate various satellite-based phenology products (e.g., global MODIS/VIIRS LSP), develop phenological models, and analyze climate impacts on terrestrial ecosystems.

Time series of stock indices usually exhibit nonstationary and chaotic behavior. Analysis of the characteristics of the business cycle can reveal pertinent insights into the evolution of the stock volatility. This paper studies the characteristic periods of three main Chinese stock indices, i.e., the Shanghai composite index (SHCI), the Shenzhen component index (SZCI), and the Hang Seng index (HSI). We propose an approach based on the successive one-sided Hodrick-Prescott (SOHP) filtering and wavelet analysis of the empirical data from the stock markets, to detect their characteristic periods. In particular, the SOHP filter, which preprocesses the time series with a moving-horizon optimization procedure, enables us to extract the volatility cycles in different time scales from a stock time series and reduce noise distortion. The characteristic period of the stock index is then determined by the maxima of the wavelet power spectrum of the filtered data. The evolution of the characteristic period in time demonstrates rich information concerning the period stability of the stock market, as well as the cause and effect of the stock crash. To facilitate solving the moving-horizon optimization issue of the SOHP filter, we also present an incremental HP filtering algorithm, which greatly simplifies the involved inverse matrix operation in the HP-type filters.

Rehmannia glutinosa is one of the most important medicinal plants in China and is affected by viral diseases. In this study, a new virus tentatively named Rehmannia Allexivirus virus (ReAV) was identified through high-throughput sequencing, reverse-transcription polymerase chain reaction (RT-PCR), and Sanger sequencing. The complete genome length was 7297 nt and it contained five open reading frames (ORFs) encoding replicase, triple gene block 1(TGB1), TGB2, TGB3, and coat protein (CP). The replicase and CP presented nucleotide homology ranges of 59.9–65.2% and 47.5–55.5% between the nine ReAV isolates and the other 12 species of the genus Allexivirus. In the nine isolates, ReAV-20 and ReAV-31 isolates showed breakpoints in the replicase and CP regions, respectively. The other isolates shared 87.2–96.5% nt with the whole genome nucleotide identity. The phylogenetic tree showed that seven ReAV isolates based on replicase, CP, and whole genome sequences were clustered in the same branch and were related to the genus Allexivirus. The ReAV detection rates for 60 R. glutinosa samples were 73.3–81.7% through RT-PCR using primers targeting the replicase or CP genes. These results demonstrate that ReAV is the dominant virus in R. glutinosa. This study provides important evidence for understanding viruses infecting R. glutinosa and for establishing efficient strategies to prevent viral spread.

Background & Aims: Gamma delta (γδ) T cells are heterogeneous and functionally committed to producing interferon (IFN)-γ and interleukin (IL)-17. γδT cells are defined as tissue-resident lymphocytes in barrier tissues. Among them, IL-17–producing γδT cells are relatively abundant in the liver. However, a systematic and comprehensive understanding of the residency characteristics and function of hepatic IL-17A+ γδT cells is lacking. Methods: We undertook a single-cell analysis of γδT17 cells derived from murine livers. A parabiosis model was used to assess tissue residency. Fluorescence-activated cell sorting and adoptive transfer experiments were used to investigate the response and protective role of liver-resident CD44hiCD27− γδT cells in Listeria monocytogenes infection. Transwell assay was used to assess the role of macrophages in the chemotaxis of liver-resident CD44hiCD27− γδT cells. Results: We identified hepatic IL-17A–producing γδT cells as CD44hiCD27− γδT cells. They had tissue-resident characteristics and resided principally within the liver. Vγ6+ T cells also exhibited liver-resident features. Liver-resident CD44hiCD27− γδT cells had significantly increased proliferation capacity, and their proportion rapidly increased after infection. Some CD44hiCD27− γδT cells could produce IL-17A and IFN-γ simultaneously in response to Lm infection. Adoptive transfer of hepatic CD44hiCD27− γδT cells into Lm-infected TCRδ−/− mice led to markedly lower bacterial numbers in the liver. Hepatic macrophages promoted the migration and accumulation of liver-resident CD44hiCD27− γδT cells into infection sites. Conclusions: Liver-resident CD44hiCD27− γδT cells protect against Lm infection. Hepatic macrophages coordinate with liver-resident CD44hiCD27− γδT cells and contribute to the clearance of Lm at the early stage of infection corporately.

Abstract Background Esophageal cancer patients can experience co-occurring, related symptoms labeled symptom clusters. This study aimed to identify symptom clusters and explore which SCs independently affect the quality of life (QoL) among esophageal cancer patients. Methods This cross-sectional study was performed in Shenyang, China, from February 2021 to February 2022. Finally, 118 esophageal cancer patients effectively completed the survey. Questionnaires’ information included the Functional Assessment of Cancer Therapy-General (FACT-G), the MD Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI), the Multidimensions Scale of Perceived Social Support, and demographic and clinical characteristics. Exploratory factor analysis with principal axis factoring was used to identify symptom clusters, and multiple regression analysis was employed to analyze the influencing factors of QoL. Results The mean score of FACT-G was 69.88 (SD = 17.85) among 118 esophageal cancer patients. Four symptom clusters were identified: psychological-somatic, dysphagia, fatigue-pain, and gastrointestinal symptom clusters. Results of regression analysis indicated a significant impact on QoL for chemotherapy (β = 0.140, P

Abstract Logistic regression analysis has widespread applications in clinical disease diagnosis, but it has not yet been applied to assess the acceptance of radiotherapy and chemotherapy in patients with lung cancer. A prediction model was established to investigate the influencing factors of radiotherapy and chemotherapy in lung cancer patients in order to provide useful information for clinicians to develop targeted and effective treatment. A sample was admitted of lung cancer patients to Binzhou Medical University Hospital stays from January 2020 to June 2021. After investigating doctors, nurses, patients, managers and conducting expert demonstration, the questionnaire was formed. The questionnaire was filled out by the patient or the patient's family members. The factors in the questionnaire data of patients accepting and not accepting radiotherapy and chemotherapy were compared for univariate analysis, and the significantly different single factor were analyzed by multifactor logistic regression analysis, explored the influencing factors of radiotherapy and chemotherapy in lung cancer patients established a predictive model and drew the receiver operating characteristic curve (ROC curve). The factors of two groups had statistically significant differences or no statistically significant differences. After multifactor logistic regression analysis was conducted, own personality, self-care ability, disease course classification, own attitude towards disease treatment, and family attitude towards disease treatment were included in the influencing factors of radiotherapy and chemotherapy in patients with lung cancer. Then, a predictive model was established. The area under the ROC curve of the predicted model was 0.973, the 95% confidence interval was 0.952–0.995, the optimal critical value was 0.832, the sensitivity was 91.84%, the specificity was 89.09%, and the accuracy was 90.85%. Based on logistic regression analysis, the prediction model could predict the extent of accepting radiotherapy and chemotherapy in patients with lung cancer. Understanding the factors related to patients with lung cancer accepting radiotherapy and chemotherapy could provide useful information for the targeted and effective treatment by clinicians.

In the present work, a deep learning-based network called LeNet is applied for accurate grassland map production from Sentinel-2 data for the Greater Sydney region, Australia. First, we apply the technique to the base date Sentinel-2 data (non-seasonal) to make the vegetation maps. Then, we combine short time-series (seasonal) data and enhanced vegetation index (EVI) information to the base date imagery to improve the classification results and generate high-resolution grassland maps. The proposed model obtained an overall accuracy (OA) of 88.36% for the mono-temporal data, and 92.74% for the multi-temporal data. The experimental products proved that, by combining the short time-series images and EVI information to the base date, the classification maps' accuracy is increased by 4.38%. Moreover, the Sentinel-2 produced grassland maps are compared with the pre-existing maps such as Australian Land Use and Management (ALUM) 50 m resolution and Dynamic Land Cover Dataset (DLCD) with 250 m resolution as well as some traditional machine learning methods such as Support Vector Machine (SVM) and Random Forest (RF). The results show the effect of the LeNet network's performance and efficiency for grassland map production from short time-series data. As a result, decision-makers and urban planners can benefit from this work in terms of grassland change identification, monitoring, and planning assessment.

Background Elevated estradiol (E2) levels are an inevitable outcome of the controlled ovulation hyperstimulation. However, the effect of this change on pregnancy is still uncertain. Our study aimed to analyze the impact of increased serum E2 at the day of human chorionic gonadotropin (hCG) administration on the clinical outcomes of women with fresh embryo transfer (ET) cycles. Methods This study included 3,009 fresh ET cycles from October 2015 to September 2021. Based on the stage of embryos transferred, these cycles were categorized into the cleavage group and blastocyst group. Both groups were then divided into four sets according to E2 levels when hCG was administered: set 1 (E2 ≤ 2,000 pg/ml), set 2 (E2 = 2,001–3,000 pg/ml), set 3 (E2 = 3,001–4,000 pg/ml), and set 4 (E2 > 4,000 pg/ml). The primary outcome was the clinical pregnancy rate (CPR). Binary logistics regression analysis was established to explore the association between CPR and E2 levels. Specifically, the threshold effect of serum E2 on CPR was revealed using the two-piecewise linear regression analyses. Results The multivariate regression model in the cleavage group showed that patients’ CPR in set 4 was 1.59 times higher than those in reference set 1, but the statistical difference was insignificant (P = 0.294). As for the blastocyst group, patients in set 4 had a lower CPR with adjusted ORs of 0.43 (P = 0.039) compared to patients in set 1. The inflection point for the blastocyst group was 39.7 pg/dl according to the results of the two-piecewise linear regression model. When E2 levels were over the point, the CPR decreased by 17% with every 1 pg/dl increases in serum E2 (adjusted OR = 0.83, 95% CI [0.72–0.96], P = 0.012). Conclusions Elevated E2 levels (>39.7 pg/dl) on hCG trigger day were associated with decreased CPR in patients with fresh blastocyst ET. However, it had no similar effect on the CPR of patients with fresh cleavage-stage ET.

Forecasting the amplitude and timing of the sunspot cycle is highly important for solar physics and space weather applications, but high-precision prediction of solar magnetic activity has remained an outstanding challenge. The Informer model, as the most advanced deep learning technique, is an ideal approach for predicting solar activity cycle. Using the whole-disk sunspot numbers (SSNs) between 1749 and 2023 and the hemispheric SSNs between 1992 and 2023, the amplitudes and timings of Solar Cycles 25 and 26 are predicted by the Informer model. The main results are the following: (1) the activity levels of Solar Cycles 25 and 26 continue being weak-moderate cycles with their strengths stronger than Solar Cycle 24, implying that the long-term solar variability is significantly modulated in length and magnitude by the Gleissberg century cycle; (2) the Gnevyshev peaks of Solar Cycles 25 and 26 are clearly observed with a higher value in the second peak, suggesting that the numbers of the large sunspot groups are greater compared to the small sunspot groups in these two cycles; and (3) during Solar Cycle 25, the activity level in the southern hemisphere is predicted to be stronger than that in the northern one, revealing significant asymmetry and asynchronization between the two hemispheres. Our analysis results show that solar cycle predictions can be made more accurate if performed separately for each hemisphere. Furthermore, Solar Cycles 25 and 26 are likely to be weak-moderate cycles, in agreement with the precursor-based and model-based prediction methods.

Abstract Targeting cancer cells with high specificity is one of the most essential yet challenging goals of tumor therapy. Because different surface receptors, transporters, and integrins are overexpressed specifically on tumor cells, using these tumor cell‐specific properties to improve drug targeting efficacy holds particular promise. Targeted fluorescent prodrugs not only improve intracellular accumulation and bioavailability but also report their own localization and activation through real‐time changes in fluorescence. In this review, efforts are highlighted to develop innovative targeted fluorescent prodrugs that efficiently accumulate in tumor cells in different organs, including lung cancer, liver cancer, cervical cancer, breast cancer, glioma, and colorectal cancer. The latest progress and advances in chemical design and synthetic considerations in fluorescence prodrug conjugates and how their therapeutic efficacy and fluorescence can be activated by tumor‐specific stimuli are reviewed. Additionally, novel perspectives are provided on strategies behind engineered nanoparticle platforms self‐assembled from targeted fluorescence prodrugs, and how fluorescence readouts can be used to monitor the position and action of the nanoparticle‐mediated delivery of therapeutic agents in preclinical models. Finally, future opportunities for fluorescent prodrug‐based strategies and solutions to the challenges of accelerating clinical translation for the treatment of organ‐specific tumors are proposed.

Abstract Faeces Vespertilionis is a commonly used fecal traditional Chinese medicine. Traditionally, it is identified relying only on morphological characters. This poses a serious challenge to the composition analysis accuracy of this complex biological mixture. Thus, for quality control purposes, an accurate and effective method should be provided for taxonomic identification of Faeces Vespertilionis. In this study, 26 samples of Faeces Vespertilionis from ten provinces in China were tested using DNA metabarcoding. Seven operational taxonomic units (OTUs) were detected as belonging to bats. Among them, Hipposideros armiger (Hodgson, 1835) and Rhinolophus ferrumequinum (Schober and Grimmberger, 1997) were the main host sources of Faeces Vespertilionis samples, with average relative abundances of 59.3% and 24.1%, respectively. Biodiversity analysis showed that Diptera and Lepidoptera were the most frequently consumed insects. At the species level, 19 taxa were clearly identified. Overall, our study used DNA metabarcoding to analyze the biological composition of Faeces Vespertilionis, which provides a new idea for the quality control of this special traditional Chinese medicine.

This study mainly verified the influences of personality traits on students’ academic achievements and assessed the mediating effects of major identity and self-efficacy, under the classical model of chain mediating effects, with the data of business major students. The results show that both extraversion and conscientiousness have positive total effect on students’ academic achievements, and they are mainly realized through the chain mediating effects of self-efficacy and major identity to self-efficacy, and are mainly based on self-efficacy mediating effect, which is more obvious in the dimension of behavioral efficacy. Openness also affects academic achievement through a self-efficacy mediating effect and major identity to self-efficacy chain mediating effect, but the degree of influence is weak, and the total effect is not significant; the overall effect of agreeableness personality on academic achievement is negative, and it is mainly reflected through direct effect. This finding suggests that academic achievement does not reflect students’ team ability and performance.

Activation of the stimulator of interferon gene (STING)-mediated innate immune response has been suggested as a promising therapeutic strategy for cancers. However, the effects of STING agonist on natural killer (NK) cell-mediated anti-tumor responses in pancreatic cancer remains unknown. Herein, we evaluated the effects of a classical STING agonist cyclic GMP-AMP (cGAMP) on NK cells in pancreatic cancer. We found that cGAMP could directly activate NK cells and enhance the sensitivity of pancreatic cancer cells to NK cell cytotoxicity, suggesting that cGAMP may become a potential adjuvant for NK cell therapy. In addition, combination of CAR-NK-92 cells targeting mesothelin and cGAMP displayed greater antitumor efficacy by inhibiting tumor growth and prolonging survival of the mouse model of pancreatic cancer. These results suggest that the combination of a STING agonist and NK cells may become a novel immunotherapy strategy for pancreatic cancer.

Abstract Gleditsia sinensis is an endemic species widely distributed in China with high economic and medicinal value. To explore the genomic evolution and phylogenetic relationships of G. sinensis, the complete mitochondrial (mt) genome of G. sinensis was sequenced and assembled, which was firstly reported in Gleditsia. The mt genome was circular and 594,121 bp in length, including 37 protein-coding genes (PCGs), 19 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. The overall base composition of the G. sinensis mt genome was 27.4% for A, 27.4% for T, 22.6% for G, 22.7% for C. The comparative analysis of PCGs in Fabaceae species showed that most of the ribosomal protein genes and succinate dehydrogenase genes were lost. In addition, we found that the rps4 gene was only lost in G. sinensis, whereas it was retained in other Fabaceae species. The phylogenetic analysis based on shared PCGs of 24 species (22 Fabaceae and 2 Solanaceae) showed that G. sinensis is evolutionarily closer to Senna species. In general, this research will provide valuable information for the evolution of G. sinensis and provide insight into the phylogenetic relationships within the family Fabaceae.

Variations across cells, modules, packs, and vehicles can cause significant errors in the state estimation of LIBs using machine learning algorithms, especially when trained with small datasets. Training with large datasets that account for all variations is often impractical due to resource and time constraints at initial product release. To address this issue, we proposed a novel architecture that leverages electronic control units, edge computers, and the cloud to detect unrevealed variations and abnormal degradations in LIBs. The architecture comprised a generalized deep neural network (DNN) for generalizability, a personalized DNN for accuracy within a vehicle, and a detector. We emphasized that a generalized DNN trained with small datasets must show reasonable estimation accuracy during cross validation, which is critical for real applications before online training. We demonstrated the feasibility of the architecture by conducting experiments on 65 DNN models, where we found distinct hyperparameter configurations. The results showed that the personalized DNN achieves a root mean square error (RMSE) of 0.33%, while the generalized DNN achieves an RMSE of 4.6%. Finally, the Mahalanobis distance was used to consider the SOH differences between the generalized DNN and personalized DNN to detect abnormal degradations.

Abstract. Introduction:. The objective of this study was to explore the clinical, laboratory, and imaging features of severe Chlamydia psittaci pneumonia in order to improve early diagnosis and treatment success rates. Methods:. We conducted a retrospective record review of 14 cases of severe Chlamydia psittaci pneumonia diagnosed by metagenomic next-generation sequencing technology in our hospital. We extracted and analyzed data on the clinical symptoms and signs, contact history, laboratory investigations, chest computed tomography, treatment, and clinical outcomes. Results:. Of the 14 patients, 12 (86%) were male and two (14%) were female, with a mean age of 57 years (SD: 7 years). Eleven patients (79%) had a history of poultry contact. The main clinical manifestations were fever (n = 14, 100%), flu-like symptoms (n = 10, 71%), cough, sputum (n = 9, 64%), and dyspnea (n = 5, 36%). Blood tests revealed marked elevation of neutrophil percentage, C-reactive protein, procalcitonin, brain natriuretic peptide, and creatine kinase levels; slight elevation of aspartate aminotransferase, creatinine, urea, fibrinogen, and D-dimer levels; and decreased albumin, sodium, and calcium levels. Chest computed tomography showed bilateral lesions (n = 7, 50%), middle-lower lobe lesions (n = 10, 71%), lesions in multiple lobes (n = 9, 64%), consolidation shadows (n = 11, 79%), and pleural effusions (n = 11, 79%). The median time from disease onset to hospital admission was 4.5 days (interquartile range: 1–17 days); the mean length of hospital stay was 20.9 ± 8.5 days, and the mean time from admission to diagnosis was 5.1 ± 2.6 days. After diagnosis, patients were either treated with doxycycline alone or doxycycline combined with quinolones. All 14 patients developed respiratory failure and received invasive mechanical ventilation; two (14%) received veno-venous extracorporeal membrane oxygenation, four (29%) received continuous renal replacement therapy, and three (21%) died. Discussion and conclusion:. A poultry contact history and typical flu-like symptoms are early indicators of Chlamydia psittaci pneumonia. Substantial elevations in procalcitonin, creatine kinase, and brain natriuretic peptide indicate severe disease. Metagenomic next-generation sequencing is useful for diagnosis. Early empirical antibiotic therapy with quinolones can reduce the mortality in critically ill patients.

Researchers have conducted many studies on the relationship between external rewards and intrinsic motivation. A recent study showed that, compared with delayed rewards, rewards delivered immediately after the experiment enhanced the participants’ intrinsic motivation. However, this study did not rule out the possibility of a misattribution effect of extrinsic motivation. The present research conducted three studies to explore whether immediate rewards actually enhance intrinsic motivation. To rule out the interference of the misattribution effect of extrinsic motivation, according to the different characteristics of extrinsic motivation and intrinsic motivation, Study 1 and Study 2 improved the prior experimental paradigm, and the results indicated that the intrinsic motivation of participants who received extra rewards immediately after completing experimental tasks was stronger than that of participants who received the delayed extra reward. Furthermore, to rule out the potential interference of temporal discounting, Study 3 introduced a new variable—reward magnitude. The results showed that the delivery time of the extra reward had an independent effect on intrinsic motivation and that the immediacy of the extra reward could enhance intrinsic motivation. In all, the three studies strongly demonstrated that immediate external extra rewards could truly enhance intrinsic motivation.

Background: Burn injury accidents happen in our daily life, and the burn mortality is especially high in the low-to-middle-income countries. Camellia cake extracts (CCEs) are compound extracts from Camellia cake, and the major ingredients in CCEs may have antimicrobial, anti-oxidative, and anti-inflammatory effects. However, the effects of CCEs on burn inflammation and injury remain unknown. Objective: This study is to investigate the effects of CCEs in burn injury and explore its mechanism. Design: First, CCEs were identified to mainly contain camelliaside A and B using Ultra High Performance Liquid Chromatography-Time of Flight Mass Spectrometer (UHPLC-TOF-MS) method. Second, the CCEs’ effect on burn was tested. Burn was induced by boiling water in mice, and then CCEs (30, 50, and 100 mg/mL) were applied on the damaged skin at 3, 7, and 14 days after burn induction. Results: The results showed that CCEs protected the skin from burn-induced inflammation and enhanced the wound healing in a dose-dependent manner. CCEs decreased the expression levels of various cytokines including IL-6, TNF-α, IL-1β, MCP-1, TGF-β, and IL-10, as well as inflammatory related factors iNOS. Moreover, CCEs increased the levels of collagens, including the mRNA of COLα-1 and COL-3, and inhibited the mRNA of MMP-1 and TIMP-1, and increased the collagen staining. CCEs also reversed the impairment of activity levels of anti-oxidative enzymes. Furthermore, CCEs suppressed the gene expression of pro-inflammatory cytokines in LPS-stimulated human skin keratinocyte, possibly through inhibiting NF-κB signaling pathway. In addition, toxicological safety experiments on CCEs showed that the oral median lethal dose (LD50) was 2,000 mg/kg, the percutaneous LD50 was greater than 2,000 mg/kg, and CCEs did not cause gene mutation. Conclusion: CCEs exert a potent anti-inflammatory effect against burn damage in mice. And toxicological safety experiments suggest that CCEs are safe for usage.

Idiopathic pulmonary fibrosis (IPF) is a disease of progressive lung fibrosis with a high mortality rate. This study aimed to uncover the underlying molecular features for different types of IPF. IPF microarray datasets were retrieved from GEO databases. Weighted gene co-expression analysis (WGCNA) was used and identified subgroup-specific WGCNA modules. Infiltration-level immune cells in different subgroups of microenvironments were analyzed with CIBERSORT algorithms. The result is we classified 173 IPF cases into two subgroups based on gene expression profiles, which were retrieved from the GEO databases. The SGRQ score and age were significantly higher in C2 than in C1. Using WGCNA, five subgroup-specific modules were identified. M4 was mainly enriched by MAPK signaling, which was mainly expressed in C2; M1, M2, and M3 were mainly enriched by metabolic pathways and Chemokine signaling, and the pathway of M5 was phagosome inflammation; M1, M2, M3, and M5 were mainly expressed in C1. Utilizing the CIBERSORT, we showed that the number of M1 macrophage cells, CD8 T cells, regulatory T cells (Tregs), and Plasma cells was significantly different between C1 and C2. We found the molecular subgroups of IPF revealed that cases from different subgroups may have their unique patterns and provide novel information to understand the mechanisms of IPF itself.

Abstract High‐capacity layered oxide Ni‐rich cathodes are attractive to enhance the driving‐range of electric vehicles because of its preferential costs. Nevertheless, in Ni‐rich cathodes, there are still many issues such as microcracks generation along grain boundaries and interface side reaction between active substance and electrolyte, resulting in the rapidly deterioration of electrochemical property. Herein, improving the performance of Ni‐based cathodes by structural regulation is summarized. The remaining challenges and outlook are discussed as well.

Thermochemical cycles have been predominantly used for energy transformation from heat to stored chemical free energy in the form of hydrogen. The thermochemical cycle based on uranium (UTC), proposed by Oak Ridge National Laboratory, has been considered as a better alternative compared to other thermochemical cycles mainly due to its safety and high efficiency. UTC process includes three steps, in which only the first step is unique. Hydrogen production apparatus with hectogram reactants was designed in this study. The results showed that high yield hydrogen was obtained, which was determined by drainage method. The results also indicated that the chemical conversion rate of hydrogen production was in direct proportion to the mass of Na2CO3, while the solid product was Na2UO4, instead of Na2U2O7. Nevertheless the thermochemical cycle used for hydrogen generation can be closed, and chemical compounds used in these processes can also be recycled. So the cycle with Na2UO4 as its first reaction product has an advantage over the proposed UTC process, attributed to the fast reaction rate and high hydrogen yield in the first reaction step. Keywords: Thermochemical cycle, Hydrogen production, Uranium, Sodium urinate, Energy

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain or discomfort. Previous studies have illustrated that the gut microbiota might play a critical role in IBS, but the conclusions of these studies, based on various methods, were almost impossible to compare, and reproducible microorganism signatures were still in question. To cope with this problem, previously published 16S rRNA gene sequencing data from 439 fecal samples, including 253 IBS samples and 186 control samples, were collected and processed with a uniform bioinformatic pipeline. Although we found no significant differences in community structures between IBS and healthy controls at the amplicon sequence variants (ASV) level, machine learning (ML) approaches enabled us to discriminate IBS from healthy controls at genus level. Linear discriminant analysis effect size (LEfSe) analysis was subsequently used to seek out 97 biomarkers across all studies. Then, we quantified the standardized mean difference (SMDs) for all significant genera identified by LEfSe and ML approaches. Pooled results showed that the SMDs of nine genera had statistical significance, in which the abundance of Lachnoclostridium, Dorea, Erysipelatoclostridium, Prevotella 9, and Clostridium sensu stricto 1 in IBS were higher, while the dominant abundance genera of healthy controls were Ruminococcaceae UCG-005, Holdemanella, Coprococcus 2, and Eubacterium coprostanoligenes group. In summary, based on six published studies, this study identified nine new microbiome biomarkers of IBS, which might be a basis for understanding the key gut microbes associated with IBS, and could be used as potential targets for microbiome-based diagnostics and therapeutics.

Supply chain integration plays an important role in the development of the vegetable industry in terms of vegetable quality, vegetable safety, and vegetable security in rural China. This paper explores how agricultural cooperatives integrate the vegetable supply chain by taking a trinity cooperative as an example in China. It explains the translation concatenation of supply chain integration for this cooperative by constructing actor networks in four development stages, including the seed stage, start-up stage, development stage, and mature stage. The findings show that supply chain integration in production cooperation, supply & sales cooperation, and credit cooperation is a useful trinity cooperative model of supply chain integration for investigating vegetable supply chain integration through internal integration and external integration. This paper suggests that cooperatives in the vegetable supply chain should facilitate close coordination among different shareholders and further improve the efficiency of supply chain integration. The government should provide training opportunities and funding to encourage cooperatives to participate in supply chain integration within the vegetable industry.

Checkpoint blockade therapy, for example using antibodies against CTLA-4 and PD-1/PD-L1, relieves T cells from the suppression by inhibitory checkpoints in the tumor microenvironment; thereby achieving good outcomes in the treatment of different cancer types. Like T cells, natural killer (NK) cell inhibitory receptors function as checkpoints for NK cell activation. Upon interaction with their cognate ligands on infected cells, tumor cells, dendritic cells and regulatory T cells, signals from these receptors severely affect NK cells' activation and effector functions, resulting in NK cell exhaustion. Checkpoint inhibition with antagonistic antibodies (Abs) can rescue NK cell exhaustion and arouse their robust anti-tumor capacity. Most notably, the response to anti-PD-1 therapy can be enhanced by the increased frequency and activation of NK cells, thereby increasing the overall survival of patients with multiple types of cancer. In addition, rescue of NK cell activity could enhance adaptive T cells' anti-tumor activity. Some antagonistic Abs (e.g., anti-TIGIT and anti-NKG2A monoclonal Abs) have extraordinary potential in cancer therapy, as evidenced by their induction of potent anti-tumor immunity through recovering both NK and T cell function. In this review, we summarize the dysfunction of NK cells in the tumor microenvironment and the key NK cell checkpoint receptors or molecules that control NK cell function. We particularly focus on recent advances in the most promising strategies through blockade of NK cell checkpoints or their combination with other approaches to more effectively reject tumors.

The popular genetically-encoded Ca2+ indicator, GCaMP, has several side-effects. Here the authors show that GCaMP containing CaM interferes with gating and signaling of L-type calcium channels, which disrupts Ca2+ dynamics and gene expression, and develop GCaMP-X to overcome these limitations.

Polycystic kidney disease 2-like 1 protein (PKD2L1) is a voltage-dependent calcium-dependent nonselective ion channel involved in sour taste perception and regulation of pH-dependent action potential of spinal cord neurons. Here the authors present the 3.4 Å cryo-EM structure of PKD2L1 in the open state and propose a model for the gating mechanism.

In this study, the complete mitochondrial genome of Asclepios apicalis was sequenced and assembled, which was first reported in Asclepios. The mitogenome of Asclepios apicalis was 15,391 bp in length, and it contained 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, 13 protein-coding genes (PCGs), and a control region (D-loop), the overall base nucleotide compositions encoded was 42.9% A, 14.3% C, 10.0% G, and 32.8% T.

Abstract Background Aging is a known risk factor of idiopathic pulmonary fibrosis (IPF). However, the pathogenic mechanisms underlying the effects of advanced aging remain largely unknown. Telomeric repeat-containing RNA (TERRA) represents a type of long noncoding RNA. In this study, the regulatory roles of TERRA on human telomeres and mitochondria and IPF epithelial injury model were identified. Methods Blood samples were collected from patients with IPF (n = 24) and matched control individuals (n = 24). The significance of clinical research on the TERRA expression correlated with pulmonary fibrosis was assessed. The expression levels of TERRA in vivo and in vitro were determined through quantitative real-time polymerase chain reaction analysis. Telomerase activity was observed using a fluorescent quantitative TRAP assay kit. The functions of telomeres, mitochondria, and associated genes were analyzed through RNA interference on TERRA. Results TERRA expression levels significantly increased in the peripheral blood mononuclear cells of IPF patients. The expression levels also exhibited a direct and significantly inverse correlation with the percentage of predicted force vital capacity, which is a physiological indicator of fibrogenesis during IPF progression. This finding was confirmed in the epithelial injury model of IPF in vitro. RNA interference on TERRA expression can ameliorate the functions of telomeres; mitochondria; associated genes; components associated with telomeres, such as telomerase reverse transcriptase, telomerase, and cell nuclear antigen, cyclin D1; and mitochondria-associated cyclin E genes, including the MMP and Bcl-2 family. The RNA interference on TERRA expression can also improve the functions of oxidative-stress-associated genes, such as reactive oxygen species, superoxide dismutase, and catalase, and apoptosis-related genes, such as cytochrome c, caspase-9, and caspase-3. Conclusions In this study, the regulation of TERRA expression on telomeres and mitochondria during IPF pathogenesis was identified for the first time. The results may provide valuable insights for the discovery of a novel biomarker or therapeutic approach for IPF treatment.

Chromium (Cr) is one of the most severe heavy metal contaminants in soil, and it seriously threatens ecosystems and human health through the food chain. It is fundamental to collect toxicity data of Cr before developing soil quality criteria/standards in order to efficiently prevent health risks. In this work, the short-term toxic effects of Cr(VI) and Cr(III) on the root growth of eleven terrestrial plants were investigated. The corresponding fifth percentile hazardous concentrations (HC5) by the best fitting species sensitivity distribution (SSD) curves based on the tenth percentile effect concentrations (EC10) were determined to be 0.60 and 4.51 mg/kg for Cr (VI) and Cr (III), respectively. Compared to the screening level values worldwide, the HC5 values in this study were higher for Cr(VI) and lower for Cr(III) to some extent. The results provide useful toxicity data for deriving national or local soil quality criteria for trivalent and hexavalent Cr.

Decorative ornamental plants have been applied as hyperaccumulators/phytoremediators to a wide spectrum of heavy metal contaminants. In this study, pot culture experiments were conducted to investigate the Sn tolerance and accumulation in Impatiens balsamina L., Mirabilis jalapa L. and Tagetes erecta L., in order to assess the possibility of these three ornamental plants to be used as phytoremediators of Sn-contaminated soil. Results show that all three plants exhibited strong tolerance to Sn contamination, and no significant visual toxicity was observed for all three plants grown under most of the Sn treatments. The amount of Sn accumulated in the three plants was positively correlated with the Sn concentration in the soil. The order of the Sn accumulative capacity was Impatiens balsamina > Mirabilis jalapa > Tagetes erecta. Impatiens balsamina and Tagetes erecta showed a low translocation ability (TF) (Impatiens balsamina showed a relatively high bioconcentration factor (BCF, Sn concentration in each part > 100 mg/kg after Sn treatment of 500 mg/kg). Meanwhile, the TF of Mirabilis jalapa was >1, and the fluorescence accumulated the most Sn. In combination with the adaptation to high concentrations of various heavy metals, these three ornamental plants are potential candidates for Sn mining tailings or contaminated soil.

γδ T cells are a distinct subset of T cells whose T cell receptors consist of γ chains and δ chains, different from conventional αβ T cells. γδ T cells are considered as a member of the innate immunity because of their non-MHC restricted antigen recognition, rapid response to invading pathogens and sense early changes of malignant cells. Upon activation, they can further promote the activation of adaptive immune cells, such as T cells and B cells, by secreting various cytokines. Thus, γδ T cells are regarded as a bridge between innate immunity and acquired immunity. γδ T cells are involved in a variety of immune response processes, including immune defense and immune surveillance against infection and tumorigenesis. γδ T cells recognize multiple tumor-associated antigens or molecules in T cell receptors (TCRs)-dependent and natural killer cell receptors (NKRs)-dependent ways. γδ T cells not only display a direct killing capacity on a variety of tumors, but also exert anti-tumor immune responses indirectly by facilitating the function of other immune cells, such as dendritic cells (DCs), B cells and CD8+ T cells. In this review, we summarize the major subpopulations, the tumor recognition mechanisms, and the anti-tumor effects of human γδ T cells, particularly the potential of γδ T cells for cancer immunotherapy.

Lapatinib and capecitabine have been widely used in the therapy of breast cancer. However, long-term use of lapatinib and capecitabine often causes the most common side effect diarrhea, which limit the medicine use. Fructus mume (F. mume) has been proved to be effective to treat chronic diarrhea with few side effects. The compounds from F. mume were extracted by using an ethanol method. Extracts of F. mume (EFM) were analyzed by HPLC. We investigated the protective effects of EFM on the diarrhea caused by lapatinib and capecitabine. From March 1st, 2016 to June 1st, 2017, 208 breast cancer patients with diarrhea caused by lapatinib and capecitabine were recruited. The patients were evenly assigned into two groups: EG group (the patients took 100 mg EFM daily) and CG group (the patients took placebo daily). The effects of EFM on diarrhea and gastrointestinal symptoms were measured by a semiquantitative method seven-point Likert scale. Overall quality of life was measured by SF-36 questionnaire and Hospital Anxiety and Depression Scale (HADS). The HPLC analysis showed that there were three components in EFM, including citric acid, 5-hydroxymethylfurfural (5-HMF), and chlorogenic acid. Breast cancer types were observed by using Hematoxylin and eosin (H&E) stain. The breast cancer can be divided into leaflet, gland and fibroblast types. Patient age, skin metastases, treatment, and grade 1 diarrhea were significant risk factors associated with for grade 2 diarrhea. EFM reduced diarrhea and gastrointestinal symptoms by reducing the average scores of the diarrhea symptom and seven-point Likert scale, and improved life quality of patients significantly by improving SF-36 scores and reducing HADS scores when compared to that in the CG group after 6-week therapy and further 4-week follow-up (P < 0.05). EFM may be a potential choice for the diarrhea therapy in breast cancer patients.

Cletus punctiger is a famous economic crop pest in China, especially for rice. Here, we first reported the complete mitochondrial genome sequence of this pest. The mitochondrial genome is 16,166 bp in length, including 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes, and 1 control region (D-Loop). The maximum likelihood (ML) phylogenetic tree confirmed that C. punctiger belonged to the Coreidae subfamily.

The polycystic TRP subfamily member PKD2-L1, in complex with PKD1-L3, is involved in physiological responses to diverse stimuli. A major challenge to understanding whether and how PKD2-L1/PKD1-L3 acts as a bona fide molecular transducer is that recombinant channels usually respond with small or undetectable currents. Here, we discover a type of Ca2+ influx-operated Ca2+ entry (ICE) that generates pronounced Ca2+ spikes. Triggered by rapid onset/offset of Ca2+, voltage, or acid stimuli, Ca2+-dependent activation amplifies a small Ca2+ influx via the channel. Ca2+ concurrently drives a self-limiting negative feedback (Ca2+-dependent inactivation) that is regulated by the Ca2+-binding EF hands of PKD2-L1. Our results suggest a biphasic ICE with opposite Ca2+ feedback regulation that facilitates sensory responses to multimodal transient stimuli. We suggest that such a mechanism may also occur for other sensory modalities and other Ca2+ channels.